A review of skeletal dysplasia research in India.

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.

Identification and characterization of 20 novel pathogenic variants in 60 unrelated Indian patients with mucopolysaccharidoses type I and type II.

Mucopolysaccharidoses (MPS), a subgroup of lysosomal storage disorders, are caused due to deficiency of specific lysosomal enzyme involved in catabolism of glycosaminoglycans. To date more than 200 pathogenic variants in the alpha-l-iduronidase (IDUA) for MPS I and ∼500 pathogenic variants in the iduronate-2-sulphatase (IDS) for MPS II have been reported worldwide. The mutation spectrum of MPS type I and MPS type II disorders in Indian population is not characterized yet. In this study, we carried out clinical, biochemical, molecular and in silico analyses to establish the mutation spectrum of MPS I and MPS II in the Indian population. We conducted molecular analysis for 60 MPS-affected patients [MPS I (n = 30) (Hurler syndrome = 17, Hurler-Scheie syndrome = 13), and MPS II (n = 30) (severe = 18, attenuated = 12)] and identified a total of 44 [MPS I (n = 22) and MPS II (n = 22)] different pathogenic variants comprising missense, nonsense, frameshift, gross deletions and splice site variants. A total of 20 [MPS I (n = 14), and MPS II (n = 6)] novel pathogenic sequence variants were identified in our patient cohort. We found that 32% of pathogenic variants detected in IDUA were recurrent and 25% in MPS II. This is the first study revealing the mutation spectrum of MPS I and MPS II patients in the Indian population.