Laboratoire d'ImmunoRhumatologie Moléculaire, Plateforme GENOMAX, INSERM UMR_S 1109, Faculté de Médecine, Fédération Hospitalo-Universitaire OMICARE, Fédération de Médecine Translationnelle de Strasbourg (FMTS), LabEx TRANSPLANTEX, Université de Strasbourg, 67085 Strasbourg, France.
European Molecular Biology Laboratory, European Bioinformatics Institute (EMBL-EBI), Wellcome Genome Campus, Cambridge CB10 1SD, UK.
Genes (Basel). 2020 Aug 31;11(9):1021. doi: 10.3390/genes11091021.
Intellectual disability (ID) is a highly heterogeneous genetic condition with more than a thousand genes described so far. By exome sequencing of two consanguineous families presenting hallmark features of ID, we identified two homozygous variants in two genes previously associated with autosomal recessive ID: (c.1966G>A; p.Asp656Asn) and (c.310T>C; p.Phe104Leu). The segregation of the variants was validated by Sanger sequencing in all family members. In silico homology modeling of wild-type and mutated proteins revealed substantial changes in the secondary structure of both proteins, indicating a possible effect on function. The identification and validation of new pathogenic and variants in two cases of autosomal recessive ID further highlight the importance of these genes in proper brain function and development.
智力障碍（ID）是一种高度异质性的遗传疾病，迄今为止已有超过一千个基因被描述。通过对两个具有 ID 典型特征的近亲家族进行外显子组测序，我们在两个先前与常染色体隐性 ID 相关的基因中发现了两个纯合变体：（c.1966G>A;p.Asp656Asn）和（c.310T>C;p.Phe104Leu）。变体的分离通过对所有家族成员进行 Sanger 测序进行了验证。野生型和突变蛋白的同源性建模表明两种蛋白的二级结构都发生了实质性变化，表明可能对功能有影响。在两个常染色体隐性 ID 病例中发现并验证了新的致病性和变体，进一步强调了这些基因在大脑正常功能和发育中的重要性。
