Genetics Research Center, University of Social Welfare and Rehabilitation Sciences, Tehran, Iran.
Kariminejad - Najmabadi Pathology & Genetics Center, Tehran, Iran.
Arch Iran Med. 2022 Dec 1;25(12):788-797. doi: 10.34172/aim.2022.124.
Ion channel dysfunction in the brain can lead to impairment of neuronal membranes and generate several neurological diseases, especially neurodevelopmental disorders.
In this study, we set out to delineate the genotype and phenotype spectrums of 14 Iranian patients from 7 families with intellectual disability (ID) and/or developmental delay (DD) in whom genetic mutations were identified by next-generation sequencing (NGS) in 7 channel-encoding genes: and . Moreover, the data of 340 previously fully reported ID and/or DD cases with a mutation in any of these seven genes were combined with our patients to clarify the genotype and phenotype spectrum in this group.
In total, the most common phenotypes in 354 cases with ID/DD in whom mutation in any of these 7 channel-encoding genes was identified were as follows: ID (77.4%), seizure (69.8%), DD (59.8%), behavioral abnormality (29.9%), hypotonia (21.7%), speech disorder (21.5%), gait disturbance (20.9%), and ataxia (20.3%). Electroencephalography abnormality (33.9%) was the major brain imaging abnormality.
The results of this study broaden the molecular spectrum of channel pathogenic variants associated with different clinical presentations in individuals with ID and/or DD.
大脑中的离子通道功能障碍可导致神经元膜损伤，并引发多种神经疾病，特别是神经发育障碍。
在这项研究中，我们着手描述 7 个家族的 14 名伊朗患者的基因型和表型谱，这些患者的智力障碍（ID）和/或发育迟缓（DD）是通过下一代测序（NGS）在 7 个通道编码基因中发现的遗传突变引起的： 和 。此外，还将 340 例以前通过对这 7 个基因中的任何一个基因突变进行全面报道的 ID 和/或 DD 病例的数据与我们的患者相结合，以阐明该组的基因型和表型谱。
在总共 354 例 ID/DD 患者中，任何一个通道编码基因突变的最常见表型如下：ID（77.4%）、癫痫（69.8%）、DD（59.8%）、行为异常（29.9%）、低张力（21.7%）、言语障碍（21.5%）、步态障碍（20.9%）和共济失调（20.3%）。脑电图异常（33.9%）是主要的脑影像学异常。
这项研究的结果拓宽了与 ID 和/或 DD 个体不同临床表现相关的通道致病变异的分子谱。
