Department of Genetics and Endocrinology, Guangzhou Women and Children's Medical Center, Guangzhou Medical University, Guangzhou, China.
Clin Genet. 2019 Jul;96(1):98-101. doi: 10.1111/cge.13559. Epub 2019 May 23.
Here we describe the second case of primary microcephaly caused by a novel homozygous splice-site variant at the NCAPD2 gene. The proband was born with microcephaly, and developed intellectual disability. Whole exome sequencing identified a canonical splice-site variant, c.3477+2T>C, at the NCAPD2 gene. Sanger sequencing showed that the proband and her sibling, a symptomatic fetus, carried a homozygous c.3477+2T>C variant, while the unaffected parents were heterozygous and her younger brother had wild-type alleles. To date, only one case of primary microcephaly with a homozygous splice-site pathogenic variant at the NCAPD2 gene has been reported. Our study of two siblings provides additional evidence that NCAPD2 is a causative gene of primary microcephaly. This finding adds new knowledge in the etiology of microcephaly and contributes to more accurate counseling of affected families.
在这里，我们描述了第二个由 NCAPD2 基因的新型纯合剪接位点变异引起的原发性小头畸形病例。先证者出生时即患有小头畸形，并伴有智力障碍。全外显子组测序发现 NCAPD2 基因的 c.3477+2T>C 经典剪接位点变异。Sanger 测序显示，先证者及其患有症状的同胞胎儿均携带纯合 c.3477+2T>C 变异，而未受影响的父母则为杂合子，其弟弟则携带野生型等位基因。迄今为止，仅报道过一例 NCAPD2 基因纯合剪接位点致病性变异导致的原发性小头畸形病例。我们对两个兄弟姐妹的研究提供了额外的证据，表明 NCAPD2 是原发性小头畸形的致病基因。这一发现增加了小头畸形病因学方面的新知识，并有助于为受影响的家庭提供更准确的咨询。
