Unique genotype-phenotype correlations within LAMA2-related limb girdle muscular dystrophy in Chinese patients

作者：Xiuli Huang, Dandan Tan, Zaiqiang Zhang, Ge Lin, Jieyu Liu, Juan Ding, Haipo Yang, Cuijie Wei, Xingzhi Chang, Yun Yuan, Chuanzhu Yan, Hui Xiong · 发表于：Frontiers in Neurology · 年份：2023 · DOI：10.3389/fneur.2023.1158094 · 被引用次数：12 · 研究领域：Genetic Neurodegenerative Diseases、Muscle Physiology and Disorders、Hereditary Neurological Disorders

Background: related limb girdle muscular dystrophy (LGMD R23) is rare. The detailed clinical phenotypes and genetic information associated with LGMD R23 are unknown. Methods: We conducted a retrospective cross-sectional and longitudinal study on 19 LGMD R23 patients. Results: Normal early motor development was observed in 84.2% patients. Mild orthopedic complications were observed in 42.1% patients. 36.8% patients had seizures, which is unusually frequent in LGMD. Epilepsy was eventually diagnosed in 26.3% patients. 46.7% patients presented with motor neuropathy. Genetic analysis identified 29 pathogenic variants, with missense and frameshift variants being the most common. The mutant sites were mainly distributed in the N-terminal and G-like domains of laminin. The missense variants are distributed near the N-terminus (exons 3-11), whereas frameshift variants are distributed in exons 12-65. Five patients were diagnosed with epilepsy and all of them harbor at least one missense variants in exon 4. 71.4% variants of patients with motor neuropathy located in the LN domain. Conclusions: variations and provides novel genotype-phenotype correlations of LGMD R23.