Expanding the clinical spectrum of biallelic ZNF335 variants.
Expanding the clinical spectrum of biallelic ZNF335 variants.
复制标题
扩大双等位 ZNF335 变体的临床谱。
DOI：
10.1111/cge.13260
复制
发表时间：
2018
影响因子：
3.5
通讯作者：
Jansen,AC
中科院分区：
文献类型：
--
作者：
Stouffs,K;Stergachis,AB;Vanderhasselt,T;Dica,A;Janssens,S;Vandervore,L;Gheldof,A;Bodamer,O;Keymolen,K;Seneca,S;Liebaers,I;Jayaraman,D;Hill,HE;Partlow,JN;Walsh,CA;Jansen,AC
ZNF335在神经发生中起重要作用，ZNF335的双等位基因变异已被确定为引起2个无关家系的严重原发性常染色体隐性小头畸形的原因。在此，我们描述了另外2个具有双等位基因ZNF 335变体的受影响个体，1个具有纯合c.1399 T > C，p.（Cys467Arg）变体的第二个体和具有复合杂合c.2171_2173delTCT，p.（Phe724del）和c.3998A > G，p.（Glu1333Gly）变体，预测后一种变体影响剪接。第1例病例表现为早期死亡和重度表型，其特征为前无脑回伴突出的轴外间隙、基底节缺失以及脑干和小脑发育不全，而第2例病例的临床表现较轻，髓鞘形成不足，MRI显示脑结构保留。我们的发现扩展了ZNF 335相关性小头畸形的临床谱。
ZNF335plays an essential role in neurogenesis and biallelic variants inZNF335have been identified as the cause of severe primary autosomal recessive microcephaly in 2 unrelated families. We describe, herein, 2 additional affected individuals with biallelicZNF335variants, 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 ofZNF335‐associated microcephaly.