Department of Fetal Medicine, Fernandez Foundation, Hyderabad, India.
Department of Anatomy, Apollo Institute of Medical Sciences and Research, Jublee Hills, Hyderabad, India.
Eur J Med Genet. 2021 Jul;64(7):104233. doi: 10.1016/j.ejmg.2021.104233. Epub 2021 Apr 30.
Primary microcephaly (MCPH) is a rare neurogenic disorder with most cases being inherited in an autosomal recessive pattern. The present report is of a case of second gravid patient with recurrent fetal microcephaly with agenesis of corpus callosum, cerebellar hypoplasia and ventriculomegaly. Maternal TORCH profile and amniotic fluid chromosomal microarray were normal. Following the termination of pregnancy, the autopsy evaluation has shown additional findings of evolving craniosynostosis, and semilobar holoprosencephaly. Whole exome sequencing done on fetal DNA from amniotic fluid, revealed a pathogenic compound heterozygous variant (NM_025009.5) c.2863C>T (p.Arg955Ter) in exon 22 and c.1372_1375del (p.Lys459SerfsTer2) in exon 11 of CEP135 gene: known to cause primary microcephaly-8; and both partners in the couple are heterozygous carriers for the same. With the identification of MCPH genes and with the availability of next-generation sequencing (NGS) based exome sequencing, a definitive prenatal diagnosis of primary microcephaly and also appropriate genetic counselling for the couple has become possible.
原发性小头畸形（MCPH）是一种罕见的神经源性疾病，大多数病例以常染色体隐性遗传模式遗传。本报告是一例第二胎孕妇的病例，其胎儿反复出现小头畸形伴胼胝体发育不全、小脑发育不良和脑室扩大。母体 TORCH 谱和羊水染色体微阵列正常。妊娠终止后，尸检评估显示出进展性颅缝早闭和半侧脑裂畸形的额外发现。对羊水胎儿 DNA 进行全外显子组测序，显示 CEP135 基因外显子 22 中的致病复合杂合变异（NM_025009.5）c.2863C>T（p.Arg955Ter）和外显子 11 中的 c.1372_1375del（p.Lys459SerfsTer2）：已知可导致原发性小头畸形-8；夫妻双方均为同一基因的杂合携带者。随着 MCPH 基因的鉴定和基于新一代测序（NGS）的外显子组测序的可用性，已经可以对原发性小头畸形进行明确的产前诊断，并为夫妻双方提供适当的遗传咨询。
