一个患有轻度儒贝尔综合征及非典型特征的巴基斯坦家族中的MKS1基因低表达突变:扩展MKS1相关纤毛病的表型谱
Hypomorphic MKS1 mutation in a Pakistani family with mild Joubert syndrome and atypical features: Expanding the phenotypic spectrum of MKS1-related ciliopathies.
作者信息
Khan Saadullah, Ullah Imran, Nasir Abdul, Meijer C Arnoud, Laurense-Bik Marlies, den Dunnen Johan T, Ruivenkamp Claudia A L, Hoffer Mariëtte J V, Santen Gijs W E, Ahmad Wasim
机构信息
Department of Biochemistry, Faculty of Biological Sciences, Quaid-i-Azam University, Islamabad, Pakistan.
Department of Biotechnology and Genetic Engineering, Kohat University of Science and Technology (KUST), Kohat, Khyber Pakhtunkhwa, Pakistan.
出版信息
Am J Med Genet A. 2016 Dec;170(12):3289-3293. doi: 10.1002/ajmg.a.37934. Epub 2016 Aug 29.
Postaxial polydactyly (PAP) is one of the most common congenital malformations observed in the general population. However, it can also occur as part of a syndrome. Unbiased genetic screening techniques such as exome sequencing are highly appropriate methods to provide a molecular diagnosis in patients with polydactyly due to the large number of mutated genes associated with it. The present study describes a consanguineous family of Pakistani origin with PAP, speech impairment, hearing impairment of variable degree, and proportionate short stature with no prominent intellectual disability or ophthalmological abnormalities. One affected individual of the family was subjected to exome sequencing which resulted in the identification of four homozygous variants including an in-frame deletion (c.1115_1117delCCT; p.(Ser372del) in MKS1, which was later shown to be the only variant segregating with the phenotype. In silico predictions supported the potential pathogenicity of the identified mutation. Additional clinical tests and MRI features of a patient in the family showed a molar tooth sign, which is a hallmark of Joubert syndrome. In conclusion, we have described a pathogenic variant in the MKS1 resulting in a mild Joubert syndrome phenotype, which broadens the spectrum of mutations in the MKS1. © 2016 Wiley Periodicals, Inc.
轴后多指畸形(PAP)是普通人群中最常见的先天性畸形之一。然而,它也可能作为综合征的一部分出现。由于与多指畸形相关的突变基因数量众多,外显子组测序等无偏倚的基因筛查技术是为多指畸形患者提供分子诊断的高度合适方法。本研究描述了一个来自巴基斯坦的近亲家庭,家庭成员患有PAP、言语障碍、不同程度的听力障碍以及匀称性身材矮小,无明显智力残疾或眼科异常。该家庭的一名受影响个体接受了外显子组测序,结果鉴定出四个纯合变异,其中包括MKS1基因中的一个框内缺失(c.1115_1117delCCT;p.(Ser372del)),后来证明这是唯一与该表型共分离的变异。计算机模拟预测支持了所鉴定突变的潜在致病性。该家庭中一名患者的额外临床检查和MRI特征显示有磨牙征,这是Joubert综合征的一个标志。总之,我们描述了MKS1基因中的一个致病变异,导致了一种轻度的Joubert综合征表型,这拓宽了MKS1基因突变的范围。© 2016威利期刊公司