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在患有多种先天性异常和发育迟缓的个体中鉴定出ARHGEF40基因第225位精氨酸残基处的错义变异。

Missense variants at the p.Arg225 residue in ARHGEF40 identified in individuals with multiple congenital anomalies and developmental delay.

作者信息

Napier Melanie P, Ryan Erin, Reich Adi, Suhl Joshua A, Masser-Frye Diane, Jones Marilyn, Beaudreau Celese, Robin Nathaniel, Goodloe Dana, Folk Leandra, Morrow Michelle M, Carere Deanna Alexis

机构信息

GeneDx LLC, Gaithersburg, MD 20877, USA.

GeneDx LLC, Gaithersburg, MD 20877, USA.

出版信息

HGG Adv. 2025 Apr 10;6(2):100408. doi: 10.1016/j.xhgg.2025.100408. Epub 2025 Jan 20.

DOI:10.1016/j.xhgg.2025.100408
PMID:39838643
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC11850187/
Abstract

The ARHGEF40 gene, also known as SOLO, encodes a RhoA-targeting guanine nucleotide exchange factor (GEF) and is currently considered a candidate gene with a potential relationship to disease. Our laboratory has confirmed variants at position p.Arg225 of the ARHGEF40 protein in multiple unrelated individuals with a phenotype including dysmorphic features, congenital anomalies and neurodevelopmental abnormalities. Here, we provide genetic and phenotypic information for two individuals harboring de novo variants at p.Arg225 and sharing a highly similar phenotype. This report suggests a relationship between variants at this amino acid position and autosomal dominant disease, and further studies will be needed to characterize this disease-gene relationship and elucidate the disease mechanism.

摘要

ARHGEF40基因，也称为SOLO，编码一种靶向RhoA的鸟嘌呤核苷酸交换因子（GEF），目前被认为是一个与疾病可能相关的候选基因。我们实验室已在多个无亲缘关系的个体中确认了ARHGEF40蛋白第225位氨基酸（p.Arg225）处的变异，这些个体具有包括畸形特征、先天性异常和神经发育异常在内的表型。在此，我们提供了两名在p.Arg225处携带新生变异且具有高度相似表型的个体的遗传和表型信息。本报告提示该氨基酸位置的变异与常染色体显性疾病之间存在关联，需要进一步研究来明确这种疾病-基因关系并阐明发病机制。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/9204/11850187/33ca6c6b4c73/gr1.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/9204/11850187/33ca6c6b4c73/gr1.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/9204/11850187/33ca6c6b4c73/gr1.jpg

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Keratin-binding ability of the N-terminal Solo domain of Solo is critical for its function in cellular mechanotransduction.Solo蛋白N端单独结构域的角蛋白结合能力对其在细胞机械转导中的功能至关重要。
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Solo, a RhoA-targeting guanine nucleotide exchange factor, is critical for hemidesmosome formation and acinar development in epithelial cells.Solo，一种 RhoA 靶向鸟嘌呤核苷酸交换因子，对于上皮细胞中的半桥粒形成和腺泡发育至关重要。
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