外显子组测序
遗传学
生物
桑格测序
先证者
无义突变
表型
外显子组
胡说
突变
复合杂合度
胼胝体发育不全
神经发育障碍
基因
胼胝体
错义突变
神经科学
作者
Alice Traversa,Enrica Marchionni,Agnese Giovannetti,Maria Luce Genovesi,Noemi Panzironi,Katia Margiotti,Giulia Napoli,Francesca Piceci‐Sparascio,Alessandro De Luca,Francesco Petrizzelli,Massimo Carella,Francesco Cardona,Silvia Bernardo,Lucia Manganaro,Tommaso Mazza,Antonio Pizzuti,Viviana Caputo
摘要
Abstract Background Corpus callosum agenesis (ACC) is one of the most frequent Central Nervous System (CNS) malformations. However, genetics underlying isolated forms is still poorly recognized. Here, we report on two female familial cases with partial ACC. The proband shows isolated partial ACC and a mild neurodevelopmental phenotype. A fetus from a previous interrupted pregnancy exhibited a complex phenotype including partial ACC and the occurrence of a de novo 17q12 microduplication, which was interpreted as probably disease‐causing. Methods A trio‐based clinical exome sequencing (CES) was performed. Results Clinical exome sequencing data analysis led to identifying a heterozygous nonsense variant (NM_139058.3:c.922G>T; NP_620689.1:p.Glu308Ter) in the aristaless related homeobox gene ( ARX ) in the proband, with a putative de novo occurrence, producing a hypothetical protein lacking two essential domains. Sanger analysis confirmed the wild‐type status of both parents in different tissues, and disclosed the occurrence of the nonsense variant in the fetus of the interrupted pregnancy, suggesting a formerly unrecognized contribution of the ARX mutation to the fetus' phenotype and gonadal or gonadosomatic mosaicism in one of the parents. Conclusion This study describes the phenotype associated with a heterozygous loss of function variant in ARX . Moreover, it highlights the importance of investigating both chromosomal and genetic contributions in cases of complex syndromic phenotypes involving CNS.
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