Hunan Provincial Maternal and Child Health Care Hospital, NO.53 Xiangchun Road, Changsha, Hunan 410008, China; NHC Key Laboratory of Birth Defects Research, Prevention and Treatment (Hunan Provincial Maternal and Child Health Care Hospital), NO.53 Xiangchun Road, Changsha, Hunan 410008, China.
Hunan Provincial Maternal and Child Health Care Hospital, NO.53 Xiangchun Road, Changsha, Hunan 410008, China; NHC Key Laboratory of Birth Defects Research, Prevention and Treatment (Hunan Provincial Maternal and Child Health Care Hospital), NO.53 Xiangchun Road, Changsha, Hunan 410008, China.
Clin Chim Acta. 2019 Apr;491:15-18. doi: 10.1016/j.cca.2019.01.007. Epub 2019 Jan 10.
Primary autosomal recessive microcephaly (MCPH) is a rare hereditary disease characterized by congenitally small with brain circumference of the head below 3 standard deviations (SD). By far, 18 MCPH genes have been reported to be associated with the disease. SASS6 gene functioned in assembly of centrioles that the majority of MCPH genes present at the centrosome. There was only research reporting a homozygous missense mutation in SASS6 gene detected in a consanguineous Pakistani family. By conducting Whole-exome sequencing (WES) and Sanger sequencing on the family trio, we identified two novel splice site mutations c.127-13A>G and c.1867+2T>A in compound heterozygous hereditary form in the SASS6 gene. The two mutations were confirmed to alter mRNA splicing by RT-PCR assay. Our finding supported the role of SASS6 in the pathogenesis of microcephaly, expanding mutation spectrums and contributing to understanding of molecular mechanisms of MCPH.
原发性常染色体隐性小头畸形（MCPH）是一种罕见的遗传性疾病，其特征是头部脑围先天较小，低于 3 个标准差（SD）。到目前为止，已经有 18 个 MCPH 基因被报道与该疾病相关。SASS6 基因在中心体中存在的大多数 MCPH 基因的中心粒组装中起作用。只有一项研究报告在一个有亲缘关系的巴基斯坦家庭中发现了 SASS6 基因的纯合错义突变。通过对家族三人进行全外显子组测序（WES）和 Sanger 测序，我们在复合杂合遗传形式中发现了 SASS6 基因中的两个新剪接位点突变 c.127-13A>G 和 c.1867+2T>A。通过 RT-PCR 检测证实这两个突变改变了 mRNA 剪接。我们的发现支持了 SASS6 在小头畸形发病机制中的作用，扩大了突变谱，并有助于理解 MCPH 的分子机制。
