Center for Medical Genetics, UZ Brussel, Brussels, Belgium.
Neurogenetics Research Unit, Reproduction Genetics and Regenerative Medicine, Vrije Universiteit Brussel, Brussels, Belgium.
Clin Genet. 2018 Aug;94(2):246-251. doi: 10.1111/cge.13260. Epub 2018 May 3.
ZNF335 plays an essential role in neurogenesis and biallelic variants in ZNF335 have been identified as the cause of severe primary autosomal recessive microcephaly in 2 unrelated families. We describe, herein, 2 additional affected individuals with biallelic ZNF335 variants, 1 individual with a homozygous c.1399 T > C, p.(Cys467Arg) variant, and a second individual with compound heterozygous c.2171_2173delTCT, p.(Phe724del) and c.3998A > G, p.(Glu1333Gly) variants with the latter variant predicted to affect splicing. Whereas the first case presented with early death and a severe phenotype characterized by anterior agyria with prominent extra-axial spaces, absent basal ganglia, and hypoplasia of the brainstem and cerebellum, the second case had a milder clinical presentation with hypomyelination and otherwise preserved brain structures on MRI. Our findings expand the clinical spectrum of ZNF335-associated microcephaly.
ZNF335 在神经发生中起着至关重要的作用，并且已经在两个不相关的家族中鉴定出 ZNF335 的双等位基因变异是严重的常染色体隐性小头症的原因。我们在此描述了另外 2 个具有双等位基因 ZNF335 变异的受影响个体，1 个个体为纯合 c.1399T>C，p.(Cys467Arg) 变异，第二个个体为复合杂合 c.2171_2173delTCT，p.(Phe724del) 和 c.3998A>G，p.(Glu1333Gly) 变异，后一种变异被预测会影响剪接。第一个病例表现为早期死亡和严重表型，其特征为前脑回无脑回，明显的轴外间隙，基底节缺失，脑桥和小脑发育不良，而第二个病例的临床表现较轻，MRI 显示脑白质发育不良，而其他脑结构则正常。我们的发现扩展了 ZNF335 相关小头症的临床谱。
