A Novel Splice Site Variant in KLHL40 Gene in Multiple Affected NEM8 Family Members Who Present Phenotypic Variability.

IF 0.9 4区医学 Q4 GENETICS & HEREDITY Molecular Syndromology Pub Date : 2025-02-01 Epub Date: 2024-08-13 DOI:10.1159/000540325

Beria Sönmez, Mehmet Kocabey, Ayşe İpek Polat, Semra Gürsoy, Pakize Karaoğlu, Rita Horvath, Katherine R Schon, Ayfer Ülgenalp, Uluç Yiş, Ahmet Okay Çağlayan, Özlem Giray Bozkaya

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引用次数: 0

Abstract

Introduction: Nemaline myopathy (NEM) is a heterogeneous muscle disease, which usually presents with hypotonia and muscle weakness. Biallelic pathogenic variants of KLHL40 gene cause severe form of NEM (NEM8), which leads to a wide range of symptoms, including hypotonia, muscle weakness, joint contractures and fractures. Nemaline bodies in muscle fiber are characteristic findings of the disease.

Case presentation: Here, we presented three affected individuals in a family with variable phenotypes, in whom the same novel splice-site variant in KLHL40 gene (c.1607+3A>T) was detected.

Discussion: This study expanded the spectrum of genotype and phenotype of NEM8, and emphasized that molecular genetic tests are highly valuable in diagnosis of patients with inconclusive muscle biopsy results.

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出现表型变异的NEM8家族成员KLHL40基因剪接位点新变异

线状肌病（NEM）是一种异质性肌肉疾病，通常表现为张力低下和肌肉无力。KLHL40基因的双等位致病变异可导致NEM （NEM8）的严重形式，导致广泛的症状，包括张力低下、肌肉无力、关节挛缩和骨折。肌纤维中的线状体是本病的特征性表现。病例介绍：在这里，我们报道了来自一个不同表型家族的三个受影响个体，他们在KLHL40基因（c.1607+3A>T）中检测到相同的新剪接位点变异。讨论：本研究扩大了NEM8的基因型和表型谱，并强调分子遗传学检测在肌肉活检结果不确定的患者诊断中具有很高的价值。

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来源期刊

Molecular Syndromology Biochemistry, Genetics and Molecular Biology-Genetics

CiteScore

1.70

自引率

9.10%

发文量

期刊介绍： ''Molecular Syndromology'' publishes high-quality research articles, short reports and reviews on common and rare genetic syndromes, aiming to increase clinical understanding through molecular insights. Topics of particular interest are the molecular basis of genetic syndromes, genotype-phenotype correlation, natural history, strategies in disease management and novel therapeutic approaches based on molecular findings. Research on model systems is also welcome, especially when it is obviously relevant to human genetics. With high-quality reviews on current topics the journal aims to facilitate translation of research findings to a clinical setting while also stimulating further research on clinically relevant questions. The journal targets not only medical geneticists and basic biomedical researchers, but also clinicians dealing with genetic syndromes. With four Associate Editors from three continents and a broad international Editorial Board the journal welcomes submissions covering the latest research from around the world.