Molecular genetics & genomic medicine · 2026
Variable Phenotypic Manifestations of Novel Compound Heterozygous CRPPA Variants in Two Iranian Siblings With Limb-Girdle Muscular Dystrophy.
СтатьяКлинический случайНазвание и аннотация: Перевод пока не подготовлен
Обработка статьи · этапы, ошибки и управление
Загрузка состояния…
Ошибки и ограничения
История · было → стало
Состояние обновляется каждые 5 секунд, пока блок открыт. Процент показывается только там, где известен объём работы. Пауза останавливает продолжение этапа; текущий запрос к источнику может завершиться.
Alagha Parnian, Ahangari Fatemeh, Kariminejad Ariana, Ghasemi Aida, Gholami Soheila, Sadatian Neda, Kariminejad Roxana, Kahrizi Kimia, Okhovat Ali Asghar, Najmabadi Hossein
Аннотация
BACKGROUND: Dystroglycanopathies are a clinically and genetically heterogeneous group of muscular dystrophies caused by impaired glycosylation of α-dystroglycan, with variants in multiple genes, including CRPPA, which is associated with a broad spectrum ranging from congenital muscular dystrophy to limb-girdle muscular dystrophy.
METHOD: The proband underwent whole exome sequencing, while Sanger sequencing was used for segregation analysis and oligonucleotide array-CGH was performed to confirm the copy number variant.
RESULTS: We report two siblings harboring an identical novel compound heterozygous CRPPA genotype, comprising a novel c.267G>C missense variant and a deletion encompassing exons 9-10. Despite sharing the same genotype, the siblings showed marked phenotypic variability. The female sibling developed childhood-onset disease with proximal weakness involving both the upper and lower limbs, whereas the male sibling presented with late-onset disease and weakness confined to the proximal lower limbs, accompanied by markedly discordant serum creatine kinase levels (1193 vs. 460 U/L).
CONCLUSION: These findings expand the mutational and clinical spectrum of CRPPA-related dystroglycanopathy, highlight marked intrafamilial phenotypic variability, and emphasize the importance of integrated single-nucleotide and copy number variant analysis in the genetic diagnosis of neuromuscular disorders.
METHOD: The proband underwent whole exome sequencing, while Sanger sequencing was used for segregation analysis and oligonucleotide array-CGH was performed to confirm the copy number variant.
RESULTS: We report two siblings harboring an identical novel compound heterozygous CRPPA genotype, comprising a novel c.267G>C missense variant and a deletion encompassing exons 9-10. Despite sharing the same genotype, the siblings showed marked phenotypic variability. The female sibling developed childhood-onset disease with proximal weakness involving both the upper and lower limbs, whereas the male sibling presented with late-onset disease and weakness confined to the proximal lower limbs, accompanied by markedly discordant serum creatine kinase levels (1193 vs. 460 U/L).
CONCLUSION: These findings expand the mutational and clinical spectrum of CRPPA-related dystroglycanopathy, highlight marked intrafamilial phenotypic variability, and emphasize the importance of integrated single-nucleotide and copy number variant analysis in the genetic diagnosis of neuromuscular disorders.