Dr. John T. Macdonald Department of Human Genetics and John P. Hussman Institute for Human Genomics, Miller School of Medicine, University of Miami, Miami, Florida, United States of America.
PLoS One. 2013 Dec 6;8(12):e82810. doi: 10.1371/journal.pone.0082810. eCollection 2013.
Autosomal recessive intellectual disability (ID) is characterized by extensive genetic heterogeneity. Recently, three mutations in SZT2 were reported in two unrelated children with unexplained infantile epileptic encephalopathy with severe ID. Here we report a European American family with three children having non-syndromic mild or moderate ID without seizures. Whole-exome sequencing of three affected siblings revealed a three base pair deletion (c.4202_4204delTTC) located in a 19 mb autozygous region on chromosome 1, leading to an amino acid deletion (p.Phe1401del) in SZT2. All three children were homozygous for the deletion and their parents were heterozygous as expected in autosomal recessive inheritance. SZT2 is highly expressed in neuronal tissues and regulates seizure threshold and neuronal excitation in mice. We conclude that the disruption of SZT2 with some residual function might lead to mild or moderate ID without seizures.
常染色体隐性智力障碍（ID）的特点是广泛的遗传异质性。最近，有报道称在两名无明显病因的婴儿癫痫性脑病伴严重 ID 的患者中发现 SZT2 的三个突变。在此，我们报告了一个欧洲裔美国家庭，其中三个孩子患有非综合征性轻度或中度 ID，无癫痫发作。对三个受影响的兄弟姐妹进行全外显子组测序发现，在 1 号染色体上一个 19mb 的常染色体纯合区域中存在三个碱基的缺失（c.4202_4204delTTC），导致 SZT2 中的一个氨基酸缺失（p.Phe1401del）。所有三个孩子均为该缺失的纯合子，而其父母则按照常染色体隐性遗传预期为杂合子。SZT2 在神经元组织中高度表达，调节小鼠的癫痫发作阈值和神经元兴奋。我们的结论是，尽管 SZT2 仍有一些残留功能，但可能导致无癫痫发作的轻度或中度 ID。
