Loss of function of PCDH12 underlies recessive microcephaly mimicking intrauterine infection
Loss of function of PCDH12 underlies recessive microcephaly mimicking intrauterine infection
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DOI：
10.1212/wnl.0000000000002704
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发表时间：
2016-05-24
期刊：
影响因子：
9.9
通讯作者：
Levy-Lahad, Ephrat
中科院分区：
文献类型：
--
作者：
Aran, Adi;Rosenfeld, Nuphar;Levy-Lahad, Ephrat
目的：确定隐性综合征的遗传基础，该综合征的特征是产前高回声脑灶、先天性小头畸形、下丘脑中脑发育不良、癫痫和严重的全面发育障碍。方法：通过全外显子组测序和纯合性图谱鉴定相关基因。结果：来自4个巴勒斯坦血缘家庭的10名患者在子宫内表现为高回声脑灶、小头畸形和胎儿宫内发育迟缓。出生后，患者出现进行性严重小头畸形、新生儿癫痫发作，几乎没有发育里程碑。脑成像显示在中脑-下丘脑-视束区域发育不良的细长肿块。对一名患病儿童的全外显子组测序显示，仅PCDH 12 c.2515C>T，p.R839X在先证者中为纯合子，并与其家族中的疾病共分离。PCDH 12 p.R839X的等位基因频率为
Objective:To identify the genetic basis of a recessive syndrome characterized by prenatal hyperechogenic brain foci, congenital microcephaly, hypothalamic midbrain dysplasia, epilepsy, and profound global developmental disability.Methods:Identification of the responsible gene by whole exome sequencing and homozygosity mapping.Results:Ten patients from 4 consanguineous Palestinian families manifested in utero with hyperechogenic brain foci, microcephaly, and intrauterine growth retardation. Postnatally, patients had progressive severe microcephaly, neonatal seizures, and virtually no developmental milestones. Brain imaging revealed dysplastic elongated masses in the midbrain-hypothalamus-optic tract area. Whole exome sequencing of one affected child revealed only PCDH12 c.2515C>T, p.R839X, to be homozygous in the proband and to cosegregate with the condition in her family. The allele frequency of PCDH12 p.R839X is