Sato Rieko, Takanashi Jun-Ichi, Tsuyusaki Yu, Kato Mitsuhiro, Saitsu Hirotomo, Matsumoto Naomichi, Takahashi Takao
Department of Pediatrics, National Hospital Organization Tokyo Medical Center, Tokyo, Japan; Department of Pediatrics, Keio University School of Medicine, Tokyo, Japan;
Department of Pediatrics, Yachiyo Medical Center, Tokyo Women's Medical University, Yachiyo, Japan;
Pediatrics. 2016 Sep;138(3). doi: 10.1542/peds.2016-0897. Epub 2016 Aug 18.
ZNF335 was first reported in 2012 as a causative gene for microcephaly. Because only 1 consanguineous pedigree has ever been reported, the key clinical features associated with ZNF335 mutations remain unknown. In this article, we describe another family harboring ZNF335 mutations. The female proband was the first child of nonconsanguineous Japanese parents. At birth, microcephaly was absent; her head circumference was 32.0 cm (-0.6 SD). At 3 months, microcephaly was noted, (head circumference, 34.0 cm [-4.6 SD]). Brain MRI showed invisible basal ganglia, cerebral atrophy, brainstem hypoplasia, and cerebellar atrophy. At 33 months, (head circumference, 41.0 cm [-5.1 SD]), she had severe psychomotor retardation. After obtaining informed consent from her parents, we performed exome sequencing in the proband and identified 1 novel and 1 known mutation in ZNF335, namely, c.1399T>C (p.C467R) and c.1505A>G (p.Y502C), respectively. The mutations were individually transmitted by her parents, indicating that the proband was compound heterozygous for the mutations. Her brain imaging findings, including invisible basal ganglia, were similar to those observed in the previous case with ZNF335 mutations. We speculate that invisible basal ganglia may be the key feature of ZNF335 mutations. For infants presenting with both microcephaly and invisible basal ganglia, ZNF335 mutations should be considered as a differential diagnosis.
ZNF335于2012年首次被报道为小头畸形的致病基因。由于仅报道过1个近亲家系，与ZNF335突变相关的关键临床特征仍不清楚。在本文中，我们描述了另一个携带ZNF335突变的家系。女性先证者是非近亲结婚的日本父母的第一个孩子。出生时无小头畸形；她的头围为32.0 cm（-0.6标准差）。3个月时发现小头畸形（头围34.0 cm [-4.6标准差]）。脑部磁共振成像显示基底神经节不可见、脑萎缩、脑干发育不全和小脑萎缩。33个月时（头围41.0 cm [-5.1标准差]），她有严重的精神运动发育迟缓。在获得其父母的知情同意后，我们对先证者进行了外显子组测序，在ZNF335中分别鉴定出1个新突变和1个已知突变，即c.1399T>C（p.C467R）和c.1505A>G（p.Y502C）。这些突变分别由她的父母遗传，表明先证者为这些突变的复合杂合子。她的脑部影像学表现，包括基底神经节不可见，与先前报道的ZNF335突变病例相似。我们推测基底神经节不可见可能是ZNF335突变的关键特征。对于同时出现小头畸形和基底神经节不可见的婴儿，应考虑ZNF335突变作为鉴别诊断。
