Abstract：
Primary microcephaly is characterized by a head circumference prenatally or at birth that falls below three standard deviations from age-, ethnic-, and sex-specific norms. Genetic defects are one of the underlying causes of primary microcephaly. Since 2014, five variants of the SASS6 gene have been identified as the cause of MCPH 14 in three reported families. In this study, we present the genetic findings of members of a nonconsanguineous Chinese couple with a history of microcephaly and fetal growth restriction (FGR) during their first pregnancy. Utilizing trio whole-exome sequencing, we identified compound heterozygous variants involving a frameshift NM_194292.3:c.450_453del p.(Lys150AsnfsTer7) variant and a splice region NM_194292.3:c.1674+3A>G variant within the SASS6 gene in the affected fetus. Moreover, reverse transcriptase-polymerase chain reaction from RNA of the mother\'s peripheral blood leukocytes revealed that the c.1674+3A>G variant led to the skipping of exon 14 and an inframe deletion. To the best of our knowledge, the association between FGR and SASS6-related microcephaly has not been reported, and our findings confirm the pivotal role of SASS6 in microcephaly pathogenesis and reveal an expanded view of the phenotype and mutation spectrum associated with this gene.
摘要：
原发性小头畸形的特征是产前或出生时的头围低于年龄的三个标准偏差-ethnic-,和性别规范。遗传缺陷是原发性小头畸形的根本原因之一。自2014年以来，在三个报道的家庭中，SASS6基因的五个变体已被确定为MCPH14的原因。在这项研究中,我们介绍了一对非血缘关系的中国夫妇在第一次怀孕期间有小头畸形和胎儿生长受限(FGR)病史。利用三重全外显子组测序，我们在受影响的胎儿中鉴定了涉及移码NM_194292.3:c.450_453delp.(Lys150AsnfsTer7)变体和SASS6基因内的剪接区NM_194292.3:c.1674+3A>G变体的复合杂合变体。此外，来自母亲外周血白细胞RNA的逆转录酶-聚合酶链反应显示c.1674+3A>G变异导致外显子14的跳跃和框内缺失。据我们所知,FGR和SASS6相关的小头畸形之间的关联尚未报道，我们的发现证实了SASS6在小头症发病机制中的关键作用，并揭示了与该基因相关的表型和突变谱的扩展视图。
