Protein-truncating mutations in ASPM cause variable reduction in brain size
Protein-truncating mutations in ASPM cause variable reduction in brain size
复制标题
DOI：
10.1086/379085
复制
发表时间：
2003-11-01
影响因子：
9.8
通讯作者：
Woods, CG
中科院分区：
文献类型：
--
作者：
Bond, J;Scott, S;Woods, CG
MCPH5基因座的ASPM基因突变被认为是人类常染色体隐性原发小头畸形症(MCPH)的最常见原因，MCPH是一种胎儿大脑正常发育失败的疾病，导致先天性小头畸形和智力低下。我们已经对10.4kb的ASPM基因进行了第一次全面的突变筛查，在23个近亲家庭的队列中鉴定了所有19个突变。突变发生在整个ASPM基因中，并被预测为蛋白质截断。51名受影响个体的表型变异发生在小头畸形的程度(低于正常的5-11个SDS)和智力低下的程度(轻度到重度)，但似乎与突变位置无关。
Mutations in the ASPM gene at the MCPH5 locus are expected to be the most common cause of human autosomal recessive primary microcephaly (MCPH), a condition in which there is a failure of normal fetal brain development, resulting in congenital microcephaly and mental retardation. We have performed the first comprehensive mutation screen of the 10.4-kb ASPM gene, identifying all 19 mutations in a cohort of 23 consanguineous families. Mutations occurred throughout the ASPM gene and were all predicted to be protein truncating. Phenotypic variation in the 51 affected individuals occurred in the degree of microcephaly (5-11 SDs below normal) and of mental retardation (mild to severe) but appeared independent of mutation position.