Terminal deletions in the long arm of chromosome 4 are an uncommon event, with a worldwide incidence of approximately 0.001%. The majority of these deletions occur de novo. Terminal deletion cases are usually accompanied by clinical findings that include facial and cardiac anomalies, as well as intellectual disability. In this study, we describe the case of a 2-year-old girl, the fourth child born to consanguineous parents. While her karyotype was normal, a homozygous deletion was identified in the chromosome 4q35.2 region by subtelomeric FISH. A heterozygous deletion of the chromosome 4q35.2 region was observed in both parents. According to the literature, this is the first report of a case that has inherited a homozygous deletion of chromosome 4qter from carrier parents. Subsequent array-CGH analyses were performed on both the case and her parents. Whole-exome sequencing was also carried out to determine potential variants. We detected a NM_001111125.3:c.2329G#x3e;T (p.Glu777Ter) nonsense variant of the IQSEC2 gene in the girl, a variant that is related to X-linked intellectual disability.
Cytogenet Genome Res

中文翻译：

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智力障碍儿童的纯合染色体 4q35.2 缺失和隐藏的 IQSEC2 致病变异共存

4 号染色体长臂末端缺失是一种不常见的事件，全球发生率约为 0.001%。大多数这些缺失是从头发生的。终末缺失病例通常伴有临床发现，包括面部和心脏异常以及智力障碍。在这项研究中，我们描述了一个 2 岁女孩的案例，这是近亲父母所生的第四个孩子。虽然她的核型正常，但通过亚端粒 FISH 在染色体 4q35.2 区域发现了纯合缺失。在父母双方中都观察到染色体 4q35.2 区域的杂合缺失。据文献报道，这是第一例从携带者父母那里遗传了染色体4qter纯合缺失的病例。随后对病例及其父母进行了阵列 CGH 分析。还进行了全外显子组测序以确定潜在的变异。我们检测到 NM_001111125.3:c.2329G#x3e;T (p.Glu777Ter) 的无意义变体女孩中的IQSEC2基因，一种与 X 连锁智力障碍有关的变异。
细胞遗传基因组研究