Department of Biotechnology and Genetic Engineering, Kohat University of Science and Technology (KUST), Kohat 26000, KP, Pakistan.
Gomal Centre of Biochemistry and Biotechnology, Gomal University, Dera Ismail Khan 29111, KP, Pakistan.
Genes (Basel). 2022 Dec 6;13(12):2299. doi: 10.3390/genes13122299.
Stuttering is a common neurodevelopment speech disorder that negatively affects the socio-psychological dimensions of people with disability. It displays many attributes of a complex genetic trait, and a few genetic loci have been identified through linkage studies. Stuttering is highly variable regarding its phenotypes and molecular etiology. However, all stutters have some common features, including blocks in speech, prolongation, and repetition of sounds, syllables, and words. The involuntary actions associated with stuttering often involve increased eye blinking, tremors of the lips or jaws, head jerks, clenched fists, perspiration, and cardiovascular changes. In the present study, we recruited a consanguineous Pakistani family showing an autosomal recessive mode of inheritance. The exome sequencing identified a homozygous splice site variant in (Armadillo Repeat Containing 3) in a consanguineous Pashtun family of Pakistani origin as the underlying genetic cause of non-syndromic stuttering. The homozygous splice site variant (NM_173081.5:c.916 + 1G > A) segregated with the stuttering phenotype in this family. The splice change leading to the skipping of exon-8 is a loss of function (LoF) variant, which is predicted to undergo NMD (Nonsense mediated decay). Here, we report as a novel candidate gene causing the stuttering phenotype. may lead to neurodevelopmental disorders, including stuttering in humans.
口吃是一种常见的神经发育性言语障碍，会对残疾人群的社会心理层面产生负面影响。它表现出许多复杂遗传特征的属性，通过连锁研究已经确定了少数几个遗传位点。口吃在表型和分子病因方面具有高度可变性。然而，所有口吃者都有一些共同的特征，包括言语中断、发音、音节和单词的延长和重复。与口吃相关的不自主动作通常包括眨眼增加、嘴唇或下巴颤抖、头部抽搐、紧握拳头、出汗和心血管变化。在本研究中，我们招募了一个表现出自体隐性遗传模式的巴基斯坦近亲家庭。外显子组测序在一个来自巴基斯坦普什图族的近亲家庭中发现了一个纯合的剪接位点变异，即（富含角蛋白重复序列 3），这是导致非综合征性口吃的潜在遗传原因。纯合剪接位点变异（NM_173081.5:c.916 + 1G > A）在这个家庭中与口吃表型共分离。导致外显子 8 跳过的剪接变化是功能丧失（LoF）变异，预计会发生 NMD（无意义介导的衰变）。在这里，我们报告 是导致口吃表型的一个新的候选基因。 可能导致神经发育障碍，包括人类的口吃。
