Zídková Jana, Kramářová Tereza, Kopčilová Johana, Réblová Kamila, Haberlová Jana, Mazanec Radim, Voháňka Stanislav, Gřegořová Andrea, Langová Martina, Honzík Tomáš, Šoukalová Jana, Ošlejšková Hana, Solařová Pavla, Vyhnálková Emílie, Fajkusová Lenka
Centre of Molecular Biology and Genetics, University Hospital Brno and Masaryk University, Brno, Czech Republic.
Department of Paediatric Neurology, 2nd Faculty of Medicine, Charles University in Prague and Motol University Hospital, Praha, Czech Republic.
Clin Genet. 2023 Nov;104(5):542-553. doi: 10.1111/cge.14407. Epub 2023 Aug 1.
Limb girdle muscular dystrophies (LGMD) are a genetically heterogeneous group of muscular dystrophies. The study presents an overview of molecular characteristics of a large cohort of LGMD patients who are representative of the Czech LGMD population. We present 226 LGMD probands in which 433 mutant alleles carrying 157 different variants with a supposed pathogenic effect were identified. Fifty-four variants have been described only in the Czech LGMD population so far. LGMD R1 caplain3-related is the most frequent subtype of LGMD involving 53.1% of patients with genetically confirmed LGMD, followed by LGMD R9 FKRP-related (11.1%), and LGMD R12 anoctamin5-related (7.1%). If we consider identified variants, then all but five were small-scale variants. One large gene deletion was identified in the LAMA2 gene and two deletions in each of CAPN3 and SGCG. We performed comparison our result with other published studies. The results obtained in the Czech LGMD population clearly differ from the outcome of other LGMD populations in two aspects-we have a more significant proportion of patients with LGMD R1 calpain3-related and a smaller proportion of LGMD R2 dysferlin-related.
肢带型肌营养不良症（LGMD）是一组具有遗传异质性的肌营养不良症。该研究概述了一大群代表捷克LGMD人群的LGMD患者的分子特征。我们展示了226例LGMD先证者，其中鉴定出433个携带157种具有假定致病效应的不同变异的突变等位基因。到目前为止，有54种变异仅在捷克LGMD人群中被描述。LGMD R1型钙蛋白酶3相关型是LGMD最常见的亚型，在基因确诊的LGMD患者中占53.1%，其次是LGMD R9型FKRP相关型（11.1%）和LGMD R12型anoctamin5相关型（7.1%）。如果考虑已鉴定的变异，那么除了五个之外都是小规模变异。在LAMA2基因中鉴定出一个大的基因缺失，在CAPN3和SGCG基因中各鉴定出两个缺失。我们将我们的结果与其他已发表的研究进行了比较。在捷克LGMD人群中获得的结果在两个方面明显不同于其他LGMD人群的结果——我们有更高比例的LGMD R1型钙蛋白酶3相关型患者和更低比例的LGMD R2型肌膜蛋白相关型患者。
