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A novel CHST3 allele associated with spondyloepiphyseal dysplasia and hearing loss in Pakistani kindred
Author(s) -
Waryah A. M.,
Shahzad M.,
Shaikh H.,
Sheikh S. A.,
Chan. A.,
Hufnagel R. B.,
Makhdoom A.,
Riazuddin S.,
Ahmed Z. M.
Publication year - 2016
Publication title -
clinical genetics
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.543
H-Index - 102
eISSN - 1399-0004
pISSN - 0009-9163
DOI - 10.1111/cge.12694
Subject(s) - short stature , exome sequencing , genetics , hearing loss , genetic heterogeneity , phenotype , kyphoscoliosis , osteochondrodysplasia , allele , medicine , consanguinity , biology , pathology , endocrinology , scoliosis , gene , audiology
Skeletal dysplasias (SDs) are highly heterogeneous disorders composed of 40 clinical sub‐types that are part of 456 well‐delineated syndromes in humans. Here, we enrolled consanguineous kindred from a remote area of Sindh province of Pakistan, with 14 affected individuals suffering with short stature, kyphoscoliosis, joint dislocations, clubfoot, heart valve anomalies and progressive bilateral mixed hearing loss. To identify pathogenic variants in this family, whole exome sequencing ( WES ) was performed in one affected and one normal individual, which revealed a novel transversion mutation (c. 802G >T; p.Glu268*) in CHST3 associated with the phenotype. CHST3 encodes a chondroitin 6‐ O ‐sulfotransferase‐1 ( C6ST ‐1) enzyme that is essential for the sulfation of proteoglycans found in cartilages. Previously, mutations in CHST3 have largely been reported in sporadic cases of SD, primarily with severe spinal abnormalities, joint dislocations, joint contractures, and clubfoot. Clinical and radiological examination of the affected individuals in this family provides new insights into phenotypic spectrum of CHST3 alleles and disease progression with age.