Journal of Postgraduate Medicine
 Open access journal indexed with Index Medicus & EMBASE  
     Home | Subscribe | Feedback  

[Download PDF
Year : 2018  |  Volume : 64  |  Issue : 2  |  Page : 98-103  

A review of skeletal dysplasia research in India

A Uttarilli1, H Shah2, A Shukla1, KM Girisha1,  
1 Department of Medical Genetics, Kasturba Medical College, Manipal University, Manipal, Karnataka, India
2 Department of Orthopedics, Kasturba Medical College, Manipal University, Manipal, Karnataka, India

Correspondence Address:
Dr. K M Girisha
Department of Medical Genetics, Kasturba Medical College, Manipal University, Manipal, Karnataka


We aimed to review the contributions by Indian researchers to the subspecialty of skeletal dysplasias (SDs). Literature search using specific keywords in PubMed was performed to retrieve all the published literature on SDs as on July 6, 2017. All published literature on SDs wherein at least one author was from an Indian institute was included. Publications were grouped into different categories based on the major emphasis of the research paper. Five hundred and forty publications in English language were retrieved and categorized into five different groups. The publications were categorized as reports based on: (i) phenotypes (n = 437), (ii) mutations (n = 51), (iii) novel genes (n = 9), (iv) therapeutic interventions (n = 31), and (v) reviews (n = 12). Most of the publications were single-patient case reports describing the clinical and radiological features of the patients affected with SDs (n = 352). We enlisted all the significant Indian contributions. We have also highlighted the reports in which Indians have contributed to discovery of new genes and phenotypes. This review highlights the substantial Indian contributions to SD research, which is poised to reach even greater heights given the size and structure of our population, technological advances, and expanding national and international collaborations.

How to cite this article:
Uttarilli A, Shah H, Shukla A, Girisha K M. A review of skeletal dysplasia research in India.J Postgrad Med 2018;64:98-103

How to cite this URL:
Uttarilli A, Shah H, Shukla A, Girisha K M. A review of skeletal dysplasia research in India. J Postgrad Med [serial online] 2018 [cited 2023 Jan 29 ];64:98-103
Available from:

Full Text


Skeletal dysplasias (SDs) are monogenic disorders of the skeletal system categorized as 42 distinct groups and accounting for at least 436 diseases.[1] Dysplasias are the conditions associated with bone and/or cartilage growth or texture.[2] Dysostoses, the conditions secondary to abnormal blastogenesis, are also included in this group since 2006.[2],[3] The birth incidence of individual SDs is very rare, but collectively the incidence is estimated to be 1 in 5000 births worldwide for all the SDs.[4] SDs contribute to significant morbidity in children and even mortality in the perinatal period. Internationally, SD is in the forefront of research in recent years. Discovery of new entities, elucidation of pathogenesis, and the underlying molecular mechanisms have increased drastically over the last few years.[5],[6] Several groups and networks [International Skeletal Dysplasia Registry (ISDR), The International Skeletal Dysplasia Society (ISDS); European Skeletal Dysplasia Network Clinical and Radiographic Management Group (ESDN-CRMG), Short Statured People of Australia Inc. (SSPA), and Little People of America (LPA)] have been working in this field to help clinicians and affected families for diagnosis and management of SDs. India, with its huge population and recent application of high-throughput genomic technologies, has started contributing to the clinical and scientific progress to understand the genetic and molecular basis of SD. At this juncture, we review the Indian contributions to this subspecialty which is poised to reach greater heights.

 Materials and Methods

A literature search was performed to retrieve all the published literature on SDs with at least one of the contributing author affiliated to an Indian center. PubMed was searched using queries {(“Osteochondrodysplasias”[MeSH]) AND “India”[MeSH], {(“Osteochondrodysplasias”[MeSH]) AND “India”[ad]}, {“Osteochondrodysplasias” AND “India”[ad]}, {“Osteochondrodysplasias” AND “India”}, {“Skeletal dysplasias” AND “India”}, and {“Skeletal dysplasia” AND “India”} as on July 6, 2017. The contribution of experts and publications of historical importance, known to the authors, were added manually. The search identified 642 publications in English language. All the abstracts were read and verified to assert their representation as publications on SDs where at least one of the contributing authors is affiliated to an institution located in India. Publications (n = 102) that did not fit into the inclusion criteria were excluded from the study [publications with (a) unavailability of either the abstracts or the full-text PDF articles (n = 59), (b) not suitable for classification under any of the category (n = 27), and (c) not true representation of SDs (n = 16) were not included]. All the remnant 540 results were categorized as reports based on: (I) phenotypes (description of clinical findings of patients without the molecular diagnosis), (II) mutations (description of the patients with a genetically confirmed skeletal dysplasia, (III) novel genes, (IV) therapeutic interventions, and (V) reviews [Table 1]. All these publications (either abstracts or full texts) were read comprehensively. The major emphasis of the publication was considered in categorizing them [Supplementary Information [SUPPORTING:1]].{Table 1}


Reports on phenotypes

We found 437 publications [case reports and series (n = 431) and novel phenotypes (n = 6)] contributed by Indians on phenotypic description of SD patients. These publications provide an estimate of SD cases in selected centers from India.

Case reports and series

Historically, three reports on phenotypes stand out from an Indian perspective. Verma and colleagues reported a new entity in six fetuses of a consanguineous family showing characteristic features of short-limbed dwarfism with severe thoracic dystrophy, micromelia, postaxial polydactyly, and genital anomalies in the males.[7],[8] This condition is now termed short-rib thoracic dysplasia-3 (SRTD3) with or without polydactyly or Verma-Naumoff syndrome (MIM#613091). The causative gene DYNC2H1 was identified subsequently.[9] In 1994, Agarwal et al. have characterized a peculiar syndrome of late-onset familial spondyloepimetaphyseal dysplasia (SEMD) termed Handigodu disease in the Chanangi and Chaluvadi communities of Karnataka (MIM%613343). This disease is inherited in an autosomal dominant condition with variable presentation.[10] However, the underlying genetic defect is not yet identified even after two decades of its first description. An unusual hand malformation syndrome known as complex camptopolydactyly was first described by Phadke et al. (MIM#607539).[11],[12] Exome sequencing performed after 14 years in the proband had eventually led to the identification of homozygous novel frameshift variation, c.220_221delinsTT in basic helix loop helix A9 (BHLHA9) gene.[13]

In 1995, a hospital-based study was conducted in Karnataka, over a 2-year period which characterized a total of 169 cases of SDs.[14] All these cases were diagnosed using clinical information, pedigree data analysis, screening of the other family members, and detailed radiological evaluation. One hundred cases were osteochondrodysplasias and the remaining were mostly dysostoses. Most of them (88%) were in pediatric age group. The highlight of this study was the report on incidence of SDs in India, which was 19.6 per 10,000 births and 5.2 per 10,000 births for lethal dysplasias. Only 7 cases could be antenatally diagnosed using ultrasound. Though this was a hospital-based study, this represents one of the largest documented series of SD from India, providing a clue to the burden of SD in India.

Nampoothiri et al. have recently published, probably the largest case series of 514 suspected SDs patients from a hospital in Kerala. The diagnostic confirmation was provided for 163 cases: enzyme analysis (54 cases) and mutation analysis (109 cases). It was highlighted that most of their patients were affected with dysostosis multiplex disorders (n = 73) followed by FGFR3 mutations (n = 49) and osteogenesis imperfecta (OI) and decreased bone density group (n = 41).[15] This study illustrates how clinical evaluation and collaborations with international colleagues can help patients and families with SD in an Indian setting.

There are two publications on large series of SDs manifesting in the neonatal period. A hospital-based study was performed over a period of 6 years on 41 North Indian patients with antenatally detected short long bones. Depending on the clinical and radiological assessment, 30 cases were suspected to be lethal.[16] This study emphasized that thanatophoric dysplasia was most common among lethal dysplasias, constituting about 20% of the cases (n = 6), whereas achondroplasia (ACH) (nonlethal dysplasias) constitutes about 27% of the total cases (n = 8). A report on analysis of 273 SD-suspected fetal autopsies from North India had identified 15 autopsied fetuses with short-limbed dwarfism.[17] This report further added that short-rib dysplasia with or without polydactyly group was the commonest dysplasia, constituting to 33% of the cases.

Evaluation of 137 patients with short stature from North India revealed that 32.1% of the total patient cohort was associated with SDs.[18] We also noted a series on clinical and radiological evaluation of 271 adult patients with SEMD tarda Handigodu type, specifically describing the radiological pattern changes in the hips.[19] The publications on clinical reports of smaller groups of patients were not detailed.

Novel phenotypes

Dating back to 1992, Phadke et al.[20] had reported a novel syndrome of metaphyseal dysplasia with multiple joint dislocations. The report of a fetus with ectrodactyly, renal aplasia, limb deformities, and Pierre Robin sequence had helped to delineate a distinct entity of acro-renal-mandibular syndrome.[21] Further characterization of acro-renal-intrauterine-mandibular syndrome was reported by another group.[22] A new phenotype involving the expression of common features of both Ellis-van Creveld and Curry-Hall syndromes with uncharacterized anomalies was reported by Gosh et al.[23] A new entity with massive cranial osteolysis, mosaic hypopigmentation, growth retardation, facial anomalies, and developmental delay was reported for the first time in a 16-month-old girl, which likely represents a Gorham-like syndrome.[24] Girisha et al. had reported a novel syndrome with overlapping clinical features of both the Larsen syndrome and Otopalatodigital syndrome.[25] However, further reports and molecular analysis are necessary for confirmation of these entities.

Reports on mutations

The molecular testing facility in several centers is recently established, as suggested by limited reports on mutations. Fifty one different reports with the clinical and molecular genetic testing of the SD patients were published to-date. It was reported that molecular analysis yields a high detection rates in the range of 41 to 98% of Indian patients affected with various SDs.[26]

Phadke et al.[27] have identified mutations in the PEX gene in 3 patients with rhizomelic chondrodysplasia punctata for the first time in India. Patients 1 and 3 showed homozygosity for 64_65delGC variant in PEX gene. Patient 2 showed homozygosity for another frame shift variant, 540_541insT in the same gene. Haplotype analysis revealed that 64_65delGC variant could be a common mutation in Indian population. The reports on the mutation analysis of the rare genetic conditions, FGFR2 mutation in Apert syndrome, DYM mutation in Dyggve-Melchoir-Clausen syndrome, CA2 mutation in osteopetrosis with renal tubular acidosis[OPTB3], EXT1 and EXT2 mutations in hereditary multiple extoses, COL1A1 mutation in Caffey disease, SOX9 missense mutation in acampomelic form of campomelic dysplasia, novel TCIRG1 mutation in malignant osteopetrosis, and PTH1R mutations with or without overt hypercalcemia in a family affected with Jansen metaphyseal chondrodysplasia were useful in understanding the molecular basis of these rare skeletal disorders.[28],[29],[30],[31],[32],[33],[34],[35] The reports on novel compound heterozygous COL27A1 mutation in Steel syndrome and homozygous LRRK1 mutation in osteosclerotic metaphyseal dysplasia observed in nonconsanguineous families were second reports, validating the cause and effect relationship for two rare SDs.[36],[37]

Nahar et al.[38] have reported the largest mutation series of 130 individuals affected with ACH. This group had suggested that all the patients with ACH were to be initially screened for the presence of two common mutations in FGFR3 gene, c.1138G>A and c.1138G>C. This was in turn proved in 81% of the sporadic ACH cases from Lucknow, India.[39] The report on molecular analysis of 60 Indian patients affected with mucopolysaccharidosis type I (MPS I; n = 30) and mucopolysaccharidosis type II (MPS II; n = 30) disorders was considerable for the presence of recurrent pathogenic variants in both the disorders.[40] Mutations in affected families of Morquio A syndrome (MPS IV A, n = 68 families, GALNS) and GM1 gangliosidosis (n = 50 families, GLB1) disorders were reported by Bidchol et al.[41],[42] They have emphasized that mutation spectrum of Morquio A syndrome patients was distinct to Indian population with high recurrence of pathogenic variants in both Morquio A syndrome and GM1 gangliosidosis (p. Ser287Leu in GALNS and c.75+2InsT in GLB1, respectively). They proposed a cost-effective means of genetic testing in Morquio A syndrome patients as they had found that 45% of the mutant alleles lie in exon 1, 7, and 8 (hotspot regions) of GALNS gene. However, in GM1 gangliosidosis the mutation spectrum was similar to other populations and 51% of the alleles screened showed pathogenic variations in exon 1, 10, and 14. Molecular genetic testing in WISP3 gene had thrown light on the private mutations in largest series of affected families with progressive pseudorheumatoid dysplasia.[43],[44] They also noted founder effect underlies several recurrent mutations. Stephen et al. had reported the largest mutation series in Indian patients affected with OI and emphasized that 71% of the mutations (25 patients) were identified in either COL1A1 or COL1A2 genes. The candidate genes for other seven consanguineous autosomal recessive OI patients were identified by homozygosity mapping using single nucleotide polymorphism (SNP) microarray and exome sequencing by Stephen et al.[45],[46] The reports on IDS mutations in 17 affected families with Hunter syndrome, ARSB mutations in 15 families of Maroteaux–Lamy syndrome, MMP2 mutations in 15 affected families with multicentric osteolysis nodulosis and arthropathy, TCIRG1 and CLCN7 mutations in 8 patients with autosomal recessive osteopetrosis, CHST3 mutations in 7 patients of recessive Larsen syndrome, CTSK mutations in 5 patients with pycnodysostosis, and EIF2AK3 nonsense mutation in five Wolcott-Rallison type of diabetes mellitus were some of the notable publications describing the respective mutation profiles in Indian patients.[47],[48],[49],[50],[51],[52],[53],[54]

Reports on novel genes

Indians researchers have started to contribute to gene discovery recently. We found nine different reports describing the rare variants in novel genes associated with SDs. Whole exome sequencing technologies in combination with or without homozygosity mapping and SNP microarray have helped in identification of various novel genes associated with rare SDs in Indian patients. Whole-genome genotyping analysis in patients with immuno-osseous dysplasia spondyloenchondrodysplasia revealed the presence of biallelic mutations in ACP5 gene.[55] Lohan et al.[56] have identified that microduplications in SHH-ZRS cause Laurin-Sandrow syndrome. The reports on association of CSPP1 mutations in Joubert syndrome with or without Jeune asphyxiating thoracic dystrophy, recurrent BGN mutations in X-linked spondylo-epi-metaphyseal dysplasia (XLR-SEMD), IFT52 variant in a human skeletal ciliopathy, and homozygous nonsense EXOC6B variant in an uncharacterized autosomal recessive SEMD with joint laxity and dislocations were some important Indian contributions.[57],[58],[59],[60] Though EXOC6B is yet to be confirmed as a cause of SD by functional studies and further reports, IFT52 is now validated by functional studies and second index case.[61] Few other reports on novel gene discovery are also noteworthy. Simsek Kiper et al.[62] have showed that a homozygous frameshift variation in sFRP4 gene was found to be associated with the Pyle's disease in humans. A synonymous splice site variant in IFT57 gene was found to be likely associated with an unclassified type of oral-facial-digital syndromes by Thevenon et al.[63] A recent report by Volpi et al.[64] had shown that heparan sulfate levels were significantly altered in patients with severe SD, immunodeficiency, and developmental delay and was caused by biallelic exostosin-like 3 (EXTL3) mutations.

Reports on therapeutic interventions

Thirty-one reports were available on either the surgical interventions or intravenous infusion of certain compounds like bisphosphonates for the treatment of some of the SDs, of which some of the significant reports were detailed in this study. A study on surgical limb lengthening for nine achondroplasia patients by Chilbule et al. showed that all the patients encountered many complications. They further emphasized that limb lengthening of more than 50% of the initial length carries significant risk.[65] A retrospective study on intramedullary rodding of long bones in 16 children with OI showed that the frequency of fractures and the related complications were dramatically reduced after careful and precise implantation of either Sheffield rods or non-elongating rods of appropriate size.[66] An interesting report by Kaur et al.[67] had highlighted the significance of combined medical management (peri- and postoperative pamidronate therapy) and surgical correction (multiple osteotomies and intramedullary fixation) of lower limb deformities in four children with OI. Oral administration of alendronate in a patient with polyostotic fibrous dysplasia was found to significantly increase the bone mineral density and result in reduction of pain and fractures.[68]


Twelve review articles summarizing the clinical, radiological, and molecular findings of different groups of SDs were available. Research progress in hereditary multiple exostoses and OI was detailed in two separate reports by Singh et al.[69],[70] Two contributions to Gene Reviews by Bhavani et al. on progressive pseudorheumatoid dysplasia and multicentric osteolytic nodular arthropathy were the only two such contributions to this widely read ebook.[71],[72]


We performed a PubMed search-based literature review of Indian contributions to the field of SDs. Most contributions are in the form of case reports describing clinical or radiological features or reports on mutations in small group of patients. However, with national and international collaborations, significant strides have been made for delineation of genotypes for several SDs. Indians have started to contribute to gene discovery as well.

Historically, Indians have contributed to the first descriptions of SRTD3 with or without polydactyly, Handigodu disease, and complex camptopolydactyly.[8],[10],[11] Recently, SRTD16 with or without polydactyly is a new SD, identified by an Indian group.[59]

The mutation series on several SDs are important contributions in understanding the genotypes of these conditions not just in India, but globally as well. Several collaborators across the country have joined hands to publish the largest series of patients with SDs, thus highlighting the strengths of Indian collaborations on monogenic disorders. Noteworthy is the mutation series in the detection of homozygous mutations in large proportion in recessive conditions, despite parents denying consanguineous marriages and presence of founder effect in recurrent mutation.[41],[42],[43],[44],[45] These studies give insights into the population structure and highly prevalent endogamy in Indians.

New gene discovery is now enabled by next generation sequencing facilities established at several centers in the country. However, scientific evidence is enhanced by collaborations to recruit more families and seeking collaborators globally for validation in cellular and animal models. These strategies have resulted in discovery of ACP5, CSPP1, BGN, IFT52, EXOC6, sFRP4, IFT57, and EXTL3 genes.[55],[56],[57],[58],[59],[60],[61],[62],[63],[64]

We might have missed out the publications not indexed using the search terms we used. Some publications not cited in PubMed would also have missed a mention here. Inadvertent omission of some contributions is also likely. However, our intention was to enlist major Indian contributions to the field of SDs that would set stage for Indian researchers to take this to new heights. With available financial, clinical, and technological resources, India is likely to contribute massively to the understanding of pathogenesis and treatment of SDs.


Indians have contributed to clinical and molecular description of SDs. This is the first comprehensive review on the subject. Recently, the trend is to define the mutation profiles in Indian patients and collaborate nationally and internationally to discover new disease phenotypes and causative genes. The next generation sequencing facilities being established in different centers across the country had helped in rapid evolvement of clinical and genetics expertise in SD research. All these efforts would eventually lead to diagnosis, care, and informed genetic counseling for affected families in India.

Financial support and sponsorship

The authors acknowledge the support provided by Department of Science and Technology - Science and Engineering Research Board (DST-SERB, India) for the project 'Application of autozygosity mapping and exome sequencing to identify genetic basis of disorders of skeletal development [SB/50/HS/005/2014]', Department of Biotechnology-Federal Ministry of Education and Research (DBT-BMBF, Germany) for 'Development and application of a next generation sequencing based gene panel for disorders with low bone mineral density [BT/IN/Germany-BMBF/05/GK/2015-16]' project, Indian Council of Medical Research (ICMR, New Delhi, India) for the project 'Clinical and molecular evaluation of inherited arthropathies and multiple vertebral segmentation defects [54/2/2013-HUM-BMS]' and all the national and international collaborators. AU has received a research grant from DST-SERB, India, towards the pursuit of National Post-Doctoral Fellowship.

Conflicts of interest

There are no conflicts of interest.


1Bonafe L, Cormier-Daire V, Hall C, Lachman R, Mortier G, Mundlos S, et al. Nosology and classification of genetic skeletal disorders: 2015 revision. Am J Med Genet A 2015;167A:2869-92.
2Offiah AC. Skeletal dysplasias: An overview. Endocr Dev 2015;28:259-76.
3Superti-Furga A, Unger S. Nosology and classification of genetic skeletal disorders: 2006 revision. Am J Med Genet A 2007;143A: 1-18.
4Orioli IM, Castilla EE, Barbosa-Neto JG. The birth prevalence rates for the skeletal dysplasias. J Med Genet 1986;23:328-32.
5Aggarwal S. Skeletal dysplasias with increased bone density: Evolution of molecular pathogenesis in the last century. Gene 2013;528:41-5.
6Panda A, Gamanagatti S, Jana M, Gupta AK. Skeletal dysplasias: A radiographic approach and review of common non-lethal skeletal dysplasias. World J Radiol 2014;6:808-25.
7Naumoff P, Young LW, Mazer J, Amortegui AJ. Short rib-polydactyly syndrome type 3. Radiology 1977;122:443-7.
8Verma IC, Bhargava S, Agarwal S. An autosomal recessive form of lethal chondrodystrophy with severe thoracic narrowing, rhizoacromelic type of micromelia, polydacytly and genital anomalies. Birth Defects Orig Artic Ser 1975;11:167-74.
9Dagoneau N, Goulet M, Genevieve D, Sznajer Y, Martinovic J, Smithson S, et al. DYNC2H1 mutations cause asphyxiating thoracic dystrophy and short rib-polydactyly syndrome, type III. Am J Hum Genet 2009;84:706-11.
10Agarwal SS, Phadke SR, Phadke RV, Das SK, Singh GK, Sharma JP, et al. Handigodu disease: A radiological study. A new variety of spondyloepi(meta)physeal dysplasia of the autosomal dominant type. Skeletal Radiol 1994;23:611-9.
11Phadke SR, Gautam P. Complex camptopolydactyly: An unusual hand malformation. Am J Med Genet 1999;83:191-2.
12Phadke SR, Agarwal S, Puri RD. Recurrence of complex camptopolydactyly in a sibling suggestive of autosomal recessive mode of inheritance. Am J Med Genet A 2003;116A:94-6.
13Phadke SR, Kar A, Bhowmik AD, Dalal A. Complex camptosynpolydactyly and mesoaxial synostotic syndactyly with phalangeal reduction are allelic disorders. Am J Med Genet A 2016;170:1622-5.
14Kulkarni ML, Samuel K, Bhagyavathi M, Sureshkumar C. Skeletal dysplasias in a hospital in southern India. Indian Pediatr 1995;32:657-65.
15Nampoothiri S, Yesodharan D, Sainulabdin G, Narayanan D, Padmanabhan L, Girisha KM, et al. Eight years experience from a skeletal dysplasia referral center in a tertiary hospital in Southern India: A model for the diagnosis and treatment of rare diseases in a developing country. Am J Med Genet A 2014;164A:2317-23.
16Kumar M, Thakur S, Haldar A, Anand R. Approach to the diagnosis of skeletal dysplasias: Experience at a center with limited resources. J Clin Ultrasound 2016;44:529-39.
17Puri RD, Thakur S, Verma IC. Spectrum of severe skeletal dysplasias in North India. Indian J Pediatr 2007;74:995-1002.
18Kaur A, Phadke SR. Analysis of short stature cases referred for genetic evaluation. Indian J Pediatr 2012;79:1597-600.
19Siddesh ND, Shah H, Joseph B. The fate of the hip in spondylo-epi-metaphyseal dysplasia: Clinical and radiological evaluation of adults with SEMD Handigodu type. Skeletal Radiol 2012;41:939-45.
20Phadke SR, Sharma AK, Agarawal SS. A new syndrome of multiple joint dislocations with metaphyseal dysplasia. Clin Dysmorphol 1993;2:264-8.
21Phadke SR, Manisha. Further delineation of acro-renal-mandibular syndrome. Clin Dysmorphol 2006;15:119-20.
22Girisha KM, Pratap D, Shah HH. Further characterization of acro-renal-uterine-mandibular syndrome: Report of a case and review of earlier reports. Clin Dysmorphol 2012;21:83-6.
23Ghosh S, Setty S, Sivakumar A, Pai KM. Report of a new syndrome: Focus on differential diagnosis and review of Ellis-van Creveld, Curry-Hall, acrofacial dysostosis, and orofacial digital syndromes. Oral Surg Oral Med Oral Pathol Oral Radiol Endod 2007;103:670-6.
24Girisha KM, Ganesh HK, Rao L, Srilatha PS. Massive cranial osteolysis, skin changes, growth retardation and developmental delay: Gorham syndrome with systemic manifestations? Am J Med Genet A 2010;152A:759-63.
25Girisha KM, Abdollahpour H, Shah H, Bhavani GS, Graham JM, Jr., Boggula VR, et al. A syndrome of facial dysmorphism, cubital pterygium, short distal phalanges, swan neck deformity of fingers, and scoliosis. Am J Med Genet A 2014;164A:1035-40.
26Garcia Segarra N, Mittaz L, Campos-Xavier AB, Bartels CF, Tuysuz B, Alanay Y, et al. The diagnostic challenge of progressive pseudorheumatoid dysplasia (PPRD): A review of clinical features, radiographic features, and WISP3 mutations in 63 affected individuals. Am J Med Genet C Semin Med Genet 2012;160C: 217-29.
27Phadke SR, Gupta N, Girisha KM, Kabra M, Maeda M, Vidal E, et al. Rhizomelic chondrodysplasia punctata type 1: Report of mutations in 3 children from India. J Appl Genet 2010;51:107-10.
28Girisha KM, Phadke SR, Khan F, Agrawal S. S252W mutation in Indian patients of Apert syndrome. Indian Pediatr 2006;43:733-5.
29Girisha KM, Cormier-Daire V, Heuertz S, Phadke RV, Phadke SR. Novel mutation and atlantoaxial dislocation in two siblings from India with Dyggve-Melchior-Clausen syndrome. Eur J Med Genet 2008;51:251-6.
30Nampoothiri S, Anikster Y. Carbonic anhydrase II deficiency a novel mutation. Indian Pediatr 2009;46:532-4.
31Vanita V, Sperling K, Sandhu HS, Sandhu PS, Singh JR. Novel EXT1 and EXT2 mutations in hereditary multiple exostoses families of Indian origin. Genet Test Mol Biomarkers 2009;13:43-9.
32Ranganath P, Laine CM, Gupta D, Makitie O, Phadke SR. COL1A1 mutation in an Indian child with Caffey disease. Indian J Pediatr 2011;78:877-9.
33Gopakumar H, Superti-Furga A, Unger S, Scherer G, Rajiv PK, Nampoothiri S. Acampomelic form of campomelic dysplasia with SOX9 missense mutation. Indian J Pediatr 2014;81:98-100.
34Siddaiahgari SR, Makadia D, Shah N, Devi RR, Lingappa L. Identification of novel mutation in autosomal recessive infantile malignant osteopetrosis. Indian J Pediatr 2014;81:969-70.
35Nampoothiri S, Fernandez-Rebollo E, Yesodharan D, Gardella TJ, Rush ET, Langman CB, et al. Jansen metaphyseal chondrodysplasia due to heterozygous H223R-PTH1R mutations with or without overt hypercalcemia. J Clin Endocrinol Metab 2016;101:4283-9.
36Kotabagi S, Shah H, Shukla A, Girisha KM. Second family provides further evidence for causation of Steel syndrome by biallelic mutations in COL27A1. Clin Genet 2017;92:323-6.
37Guo L, Girisha KM, Iida A, Hebbar M, Shukla A, Shah H, et al. Identification of a novel LRRK1 mutation in a family with osteosclerotic metaphyseal dysplasia. J Hum Genet 2017;62:437-41.
38Nahar R, Saxena R, Kohli S, Puri R, Verma IC. Molecular studies of achondroplasia. Indian J Orthop 2009;43:194-6.
39Patil SJ, Banerjee M, Phadke SR, Mittal B. Mutation analysis in Indian children with achondroplasia - utility of molecular diagnosis. Indian J Pediatr 2009;76:147-9.
40Uttarilli A, Ranganath P, Matta D, Md Nurul Jain J, Prasad K, Babu AS, et al. Identification and characterization of 20 novel pathogenic variants in 60 unrelated Indian patients with mucopolysaccharidoses type I and type II. Clin Genet 2016;90:496-508.
41Bidchol AM, Dalal A, Shah H, Suryanarayana S, Nampoothiri S, Kabra M, et al. GALNS mutations in Indian patients with mucopolysaccharidosis IVA. Am J Med Genet A 2014;164A: 2793-801.
42Bidchol AM, Dalal A, Trivedi R, Shukla A, Nampoothiri S, Sankar VH, et al. Recurrent and novel GLB1 mutations in India. Gene 2015;567:173-81.
43Bhavani GS, Shah H, Dalal AB, Shukla A, Danda S, Aggarwal S, et al. Novel and recurrent mutations in WISP3 and an atypical phenotype. Am J Med Genet A 2015;167A:2481-4.
44Dalal A, Bhavani GS, Togarrati PP, Bierhals T, Nandineni MR, Danda S, et al. Analysis of the WISP3 gene in Indian families with progressive pseudorheumatoid dysplasia. Am J Med Genet A 2012;158A:2820-8.
45Stephen J, Girisha KM, Dalal A, Shukla A, Shah H, Srivastava P, et al. Mutations in patients with osteogenesis imperfecta from consanguineous Indian families. Eur J Med Genet 2015;58:21-7.
46Stephen J, Shukla A, Dalal A, Girisha KM, Shah H, Gupta N, et al. Mutation spectrum of COL1A1 and COL1A2 genes in Indian patients with osteogenesis imperfecta. Am J Med Genet A 2014;164A: 1482-9.
47Narayanan DL, Srivastava P, Mandal K, Gambhir PS, Phadke SR. Hunter syndrome in Northern India: Clinical features and mutation spectrum. Indian Pediatr 2016;53:134-6.
48Uttarilli A, Ranganath P, Jain SJ, Prasad CK, Sinha A, Verma IC, et al. Novel mutations of the arylsulphatase B (ARSB) gene in Indian patients with mucopolysaccharidosis type VI. Indian J Med Res 2015;142:414-25.
49Bhavani GS, Shah H, Shukla A, Gupta N, Gowrishankar K, Rao AP, et al. Clinical and mutation profile of multicentric osteolysis nodulosis and arthropathy. Am J Med Genet A 2016;170A:410-7.
50Phadke SR, Fischer B, Gupta N, Ranganath P, Kabra M, Kornak U. Novel mutations in Indian patients with autosomal recessive infantile malignant osteopetrosis. Indian J Med Res 2010;131:508-14.
51Girisha KM, Bidchol AM, Graul-Neumann L, Gupta A, Hehr U, Lessel D, et al. Phenotype and genotype in patients with Larsen syndrome: Clinical homogeneity and allelic heterogeneity in seven patients. BMC Med Genet 2016;17:27.
52Mandal K, Ray S, Saxena D, Srivastava P, Moirangthem A, Ranganath P, et al. Pycnodysostosis: Mutation spectrum in five unrelated Indian children. Clin Dysmorphol 2016;25:113-20.
53Jahnavi S, Poovazhagi V, Kanthimathi S, Gayathri V, Mohan V, Radha V. EIF2AK3 mutations in South Indian children with permanent neonatal diabetes mellitus associated with Wolcott-Rallison syndrome. Pediatr Diabetes. 2014;15:313-8.
54Khare S, Goroshi MR, Budyal S, Bandgar T, Lila A, Shah N. Wolcott Rallison syndrome: A rare inherited diabetes mellitus. Indian J Pediatr 2014;81:1225-7.
55Briggs TA, Rice GI, Daly S, Urquhart J, Gornall H, Bader-Meunier B, et al. Tartrate-resistant acid phosphatase deficiency causes a bone dysplasia with autoimmunity and a type I interferon expression signature. Nat Genet 2011;43:127-31.
56Lohan S, Spielmann M, Doelken SC, Flottmann R, Muhammad F, Baig SM, et al. Microduplications encompassing the Sonic hedgehog limb enhancer ZRS are associated with Haas-type polysyndactyly and Laurin-Sandrow syndrome. Clin Genet 2014;86:318-25.
57Tuz K, Bachmann-Gagescu R, O'Day DR, Hua K, Isabella CR, Phelps IG, et al. Mutations in CSPP1 cause primary cilia abnormalities and Joubert syndrome with or without Jeune asphyxiating thoracic dystrophy. Am J Hum Genet 2014;94:62-72.
58Cho SY, Bae JS, Kim NK, Forzano F, Girisha KM, Baldo C, et al. BGN mutations in X-linked spondyloepimetaphyseal dysplasia. Am J Hum Genet 2016;98:1243-8.
59Girisha KM, Shukla A, Trujillano D, Bhavani GS, Hebbar M, Kadavigere R, et al. A homozygous nonsense variant in IFT52 is associated with a human skeletal ciliopathy. Clin Genet 2016;90:536-9.
60Girisha KM, Kortum F, Shah H, Alawi M, Dalal A, Bhavani GS, et al. A novel multiple joint dislocation syndrome associated with a homozygous nonsense variant in the EXOC6B gene. Eur J Hum Genet 2016;24:1206-10.
61Zhang W, Taylor SP, Nevarez L, Lachman RS, Nickerson DA, Bamshad M. IFT52 mutations destabilize anterograde complex assembly, disrupt ciliogenesis and result in short rib polydactyly syndrome. Hum Mol Genet 2016;25:4012-20.
62Simsek Kiper PO, Saito H, Gori F, Unger S, Hesse E, Yamana K, et al. Cortical-bone fragility: Insights from sFRP4 deficiency in Pyle's disease. N Engl J Med 2016;374:2553-62.
63Thevenon J, Duplomb L, Phadke S, Eguether T, Saunier A, Avila M, et al. Autosomal recessive IFT57 hypomorphic mutation cause ciliary transport defect in unclassified oral-facial-digital syndrome with short stature and brachymesophalangia. Clin Genet 2016;90:509-17.
64Volpi S, Yamazaki Y, Brauer PM, van Rooijen E, Hayashida A, Slavotinek A, et al. EXTL3 mutations cause skeletal dysplasia, immune deficiency, and developmental delay. J Exp Med 2017;214:623-37.
65Chilbule SK, Dutt V, Madhuri V. Limb lengthening in achondroplasia. Indian J Orthop 2016;50:397-405.
66Mulpuri K, Joseph B. Intramedullary rodding in osteogenesis imperfecta. J Pediatr Orthop 2000;20:267-73.
67Kaur S, Kulkarni KP, Kochar IS, Narasimhan R. Management of lower limb deformities in children with osteogenesis imperfecta. Indian Pediatr 2011;48:637-9.
68Khadilkar VV, Khadilkar AV, Maskati GB. Oral bisphosphonates in polyostotic fibrous dysplasia. Indian Pediatr 2003;40:894-6.
69Singh P, Mukherjee SB. Hereditary multiple exostoses, A tale of 50 years. Indian Pediatr 2015;52:795-6.
70Singh P, Seth A. Osteogenesis imperfecta: A tale of 50 years. Indian Pediatr 2015;52:1073-4.
71Bhavani GSL, Shah H, Shukla A, Dalal A, Girisha KM. Progressive pseudorheumatoid dysplasia. In: Pagon RA, Adam MP, Ardinger HH, Wallace SE, Amemiya A, Bean LJH, et al., editors. Gene Reviews(R) [Internet]. Seattle (WA) 2015: University of Washington, Seattle; 1993-2017. Available from: [Last accessed on 2017 Sep 29].
72Bhavani GSL, Shah H, Shukla A, Girisha KM. Multicentric osteolysis nodulosis and arthropathy. In: Pagon RA, Adam MP, Ardinger HH, Wallace SE, Amemiya A, Bean LJH, et al., editors. Gene Reviews(R) [Internet]. Seattle (WA) 2016: University of Washington, Seattle; 1993–2017. Available from: [Last accessed on 2017 Sep 29].

Sunday, January 29, 2023
 Site Map | Home | Contact Us | Feedback | Copyright  and disclaimer