Disruption of SPECC1L translation initiation by intragenic deletion: novel pathogenic mechanism in Teebi-hypertelorism syndrome.

IF 5.3 2区医学 Q1 GENETICS & HEREDITY

NPJ Genomic Medicine Pub Date : 2025-10-21 DOI:10.1038/s41525-025-00513-4

Arwa Babai, Daniela Oliveira, Andriana Gialeli, Malgorzata Drozniewska, Yaroslav Kainov, Cristina Dias

引用次数: 0

Abstract

Missense and loss-of-function variants in SPECC1L are associated with Teebi Hypertelorism Syndrome 1 (TBHS1). Here, we report a novel SPECC1L intragenic deletion encompassing exon 3, which contains the canonical translation start site, in two related individuals with craniofacial features consistent with TBHS1. We use functional overexpression assays to demonstrate that this deletion leads to alternative start codon usage and protein truncation. This is the first report of a SPECC1L intragenic deletion associated with TBHS1. Our findings suggest that deletion of the canonical N-terminal disordered region of SPECC1L contributes to craniofacial anomalies, warranting further investigation into its role in neural crest development.

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基因内缺失对spec1l翻译起始的破坏：tebi -远端增生综合征的新致病机制。

spec1l的错义和功能丧失变异与Teebi远距远视综合征1 （TBHS1）有关。在这里，我们报告了一个新的spec1l基因内缺失，包括包含标准翻译起始位点的外显子3，在两个颅面特征与TBHS1一致的相关个体中。我们使用功能性过表达试验来证明这种缺失导致替代起始密码子使用和蛋白质截断。这是首次报道与TBHS1相关的spec1l基因内缺失。我们的研究结果表明，spec1l的典型n端紊乱区域的缺失有助于颅面异常，需要进一步研究其在神经嵴发育中的作用。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

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来源期刊

NPJ Genomic Medicine Biochemistry, Genetics and Molecular Biology-Molecular Biology

CiteScore

9.40

自引率

1.90%

发文量

审稿时长

17 weeks

期刊介绍： npj Genomic Medicine is an international, peer-reviewed journal dedicated to publishing the most important scientific advances in all aspects of genomics and its application in the practice of medicine. The journal defines genomic medicine as "diagnosis, prognosis, prevention and/or treatment of disease and disorders of the mind and body, using approaches informed or enabled by knowledge of the genome and the molecules it encodes." Relevant and high-impact papers that encompass studies of individuals, families, or populations are considered for publication. An emphasis will include coupling detailed phenotype and genome sequencing information, both enabled by new technologies and informatics, to delineate the underlying aetiology of disease. Clinical recommendations and/or guidelines of how that data should be used in the clinical management of those patients in the study, and others, are also encouraged.