Intellectual disability (ID) is a phenotypically and genetically heterogeneous disorder. In this study, genome wide SNP microarray and whole exome sequencing are used for the variant identification in eight Pakistani families with ID. Beside ID, most of the affected individuals had speech delay, facial dysmorphism and impaired cognitive abilities. Repetitive behavior was observed in MRID143, while seizures were reported in affected individuals belonging to MRID137 and MRID175. In two families (MRID137b and MRID175), we identified variants in the genes CCS and ELFN1, which have not previously been reported to cause ID. In four families, variants were identified in ARX, C5orf42, GNE and METTL4. A copy number variation (CNV) was identified in IL1RAPL1 gene in MRID165. These findings expand the existing knowledge of variants and genes implicated in autosomal recessive and X linked ID.

中文翻译：

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外显子组测序可识别智力障碍家庭中的新突变和已知突变


智力障碍（ID）是一种表型和遗传异质性疾病。在这项研究中，使用全基因组 SNP 微阵列和全外显子组测序来鉴定 8 个巴基斯坦 ID 家族的变异。除了智力障碍之外，大多数受影响的人还存在言语迟缓、面部畸形和认知能力受损的症状。在 MRID143 中观察到重复行为，而在属于 MRID137 和 MRID175 的受影响个体中报告了癫痫发作。在两个家族（MRID137b 和 MRID175）中，我们发现了 CCS 和 ELFN1 基因的变异，此前尚未有报道称这些变异会导致 ID。在四个家族中，在 ARX、C5orf42、GNE 和 METTL4 中发现了变异。在 MRID165 的 IL1RAPL1 基因中发现了拷贝数变异 (CNV)。这些发现扩展了与常染色体隐性遗传和 X 连锁 ID 相关的变异和基因的现有知识。