Abstract：
Skeletal dysplasias are a heterogeneous group of disorders presenting mild to lethal defects. Several factors, such as genetic, prenatal, and postnatal environmental may contribute to reduced growth. Fourteen families of Pakistani origin, presenting the syndromic form of short stature either in the autosomal recessive or autosomal dominant manner were clinically and genetically investigated to uncover the underlying genetic etiology. Homozygosity mapping, whole exome sequencing, and Sanger sequencing were used to search for the disease-causing gene variants. In total, we have identified 13 sequence variants in 10 different genes. The variants in the HSPG2 and XRCC4 genes were not reported previously in the Pakistani population. This study will expand the mutation spectrum of the identified genes and will help in improved diagnosis of the syndromic form of short stature in the local population.
摘要：
骨骼发育不良是一组异质性疾病，表现出轻度至致命的缺陷。几个因素,比如遗传，产前,出生后的环境可能会导致生长减少。巴基斯坦血统的十四个家庭，临床和遗传学研究了以常染色体隐性或常染色体显性方式出现的矮小综合征形式，以揭示潜在的遗传病因。纯合性映射,整个外显子组测序，和Sanger测序用于寻找致病基因变异。总的来说,我们在10个不同基因中鉴定出13个序列变异。HSPG2和XRCC4基因的变异以前在巴基斯坦人群中没有报道。这项研究将扩大已鉴定基因的突变谱，并将有助于改善当地人群中身材矮小综合征的诊断。
