Institute for Biomedical Research and Innovation, National Research Council, 87050 Mangone, Italy.
Int J Mol Sci. 2024 Sep 26;25(19):10356. doi: 10.3390/ijms251910356.
Pathogenic variants localized in the gene coding for the Fukutin-Related Protein (FKRP) are responsible for Limb-Girdle Muscular Dystrophy type 9 (LGMDR9), Congenital Muscular Dystrophies type 1C (MDC1C), Walker-Warburg Syndrome (WWS), and Muscle-Eye-Brain diseases (MEBs). LGMDR9 is the fourth most common hereditary Limb Girdle Muscular Dystrophy in Italy. LGMDR9 patients with severe disease show an overlapping Duchenne/Becker phenotype and may have secondary dystrophin reduction on muscle biopsy. We conducted a molecular analysis of the gene by direct sequencing in 153 patients from Southern Italy (Calabria) with Duchenne/Becker-like phenotypes without confirmed genetic diagnosis. Mutational screening of the patients (112 men and 41 women, aged between 5 and 84 years), revealed pathogenic variants in 16 subjects. The most frequent variants identified were c.427C > A, p.R143S, and c.826C > A, p.L276I (NM_024301.5). The results obtained show that the Duchenne/Becker-like phenotype is frequently determined by mutations in the gene in our cohort and highlight the importance of considering LGMDR9 in the differential diagnosis of dystrophinopathies in Calabria. Finally, this study, which, to our knowledge, is the first conducted on Calabrian subjects, will contribute to the rapid identification and management of LGMDR9 patients.
致病变异位于编码 Fukutin-Related Protein（FKRP）的基因中，负责肢带型肌营养不良症 9 型（LGMDR9）、先天性肌营养不良症 1C 型（MDC1C）、沃克-沃伯格综合征（WWS）和肌肉-眼-脑疾病（MEBs）。LGMDR9 是意大利第四种常见的遗传性肢带型肌营养不良症。疾病严重的 LGMDR9 患者表现出与杜兴氏/贝克型相似的表型，肌肉活检可能存在继发的肌营养不良蛋白减少。我们对来自意大利南部卡拉布里亚地区的 153 名具有杜兴氏/贝克型表型但未经证实的遗传诊断的患者进行了基因的直接测序分子分析。对 112 名男性和 41 名女性（年龄 5 至 84 岁）患者进行了突变筛查，发现 16 名患者存在致病性变异。最常见的变异是 c.427C > A，p.R143S 和 c.826C > A，p.L276I（NM_024301.5）。研究结果表明，在我们的队列中，Duchenne/Becker 样表型常常由基因中的突变引起，这突显了在卡拉布里亚区分肌营养不良蛋白病时考虑 LGMDR9 的重要性。最后，这项研究，据我们所知，是针对卡拉布里亚人群进行的首次研究，将有助于快速识别和管理 LGMDR9 患者。
