FLNA Variants Related to Melnick-Needles Syndrome: Two Mexican Case Reports and a Comprehensive Variant Review.

IF 1.7 4区生物学 Q3 GENETICS & HEREDITY

American Journal of Medical Genetics Part A Pub Date : 2025-09-25 DOI:10.1002/ajmg.a.64246

Thania Ordaz-Robles, Jessica Vanesa Sánchez-Aguilar, Carlos Alfonso Guzmán-Martín, Sergio Saldaña-Pimentel, Ilan Vinitzky Brener, Fernando Ramírez-Jiménez, María Hortensia Valdez-de la Torre, Ghalib Bardai, Frank Rauch

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引用次数: 0

Abstract

Melnick-Needles Syndrome (MNS; OMIM #309350) is a rare X-linked dominant osteochondrodysplasia caused by FLNA gain-of-function variants. It is characterized by short stature, facial dysmorphism, skeletal anomalies, and systemic complications. FLNA encodes Filamin A, a cytoskeletal protein with over 90 binding partners. Variants in FLNA cause a broad spectrum of disorders, among which MNS represents one of the most severe phenotypes. Despite increasing research on MNS, many aspects of its genetic and phenotypic spectrum remain unknown. In this work, we presented two Mexican cases with a diagnosis of MNS with different FLNA missense variants p.(Leu1193Pro) and p.(Ser1199Leu). In addition, we performed a comprehensive review of the literature about FLNA variants related to MNS. This study reinforced the genetic and phenotypic complexity of MNS, emphasizing the critical role of exon 22 variants in the pathogenesis of the disease.

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与Melnick-Needles综合征相关的FLNA变异：两个墨西哥病例报告和一个全面的变异回顾。

Melnick-Needles综合征（MNS; omim# 309350）是一种罕见的x连锁显性骨软骨发育不良，由FLNA功能获得变异引起。它的特点是身材矮小，面部畸形，骨骼异常和全身并发症。FLNA编码丝蛋白A，一种有超过90个结合伙伴的细胞骨架蛋白。FLNA的变异引起广泛的疾病，其中MNS是最严重的表型之一。尽管对MNS的研究越来越多，但其遗传和表型谱的许多方面仍然未知。在这项工作中，我们报告了两例墨西哥病例，诊断为MNS具有不同的FLNA错义变体p.（Leu1193Pro）和p.（Ser1199Leu）。此外，我们对与MNS相关的FLNA变异的文献进行了全面的回顾。这项研究加强了MNS的遗传和表型复杂性，强调了外显子22变异在疾病发病机制中的关键作用。

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

American Journal of Medical Genetics Part A 生物-遗传学

CiteScore

3.50

自引率

5.00%

发文量

432

审稿时长

2-4 weeks

期刊介绍： The American Journal of Medical Genetics - Part A (AJMG) gives you continuous coverage of all biological and medical aspects of genetic disorders and birth defects, as well as in-depth documentation of phenotype analysis within the current context of genotype/phenotype correlations. In addition to Part A , AJMG also publishes two other parts: Part B: Neuropsychiatric Genetics , covering experimental and clinical investigations of the genetic mechanisms underlying neurologic and psychiatric disorders. Part C: Seminars in Medical Genetics , guest-edited collections of thematic reviews of topical interest to the readership of AJMG .