中国のジストロフィノグリカン症患者における創始者変異としてのCRPPAエクソン6-9欠失

Dystroglycanopathies (DGPs) are a group of muscular dystrophies with abnormal glycosylation of dystroglycan. CRPPA is a gene associated with DGPs. Understanding the genetic basis, genotype-phenotype correlations, and population-specific mutations is crucial for accurate diagnosis and genetic counseling.

To investigate CRPPA mutations in Chinese pediatric patients with DGPs, analyze genotype-phenotype correlations, and determine whether specific deletions represent founder mutations in this population.

Clinical and genetic data of pediatric patients with CRPPA-related DGPs between June 2006 and December 2023 from Peking University First Hospital were collected and analyzed. Muscle biopsy specimens from four patients were examined using immunohistochemistry, immunofluorescence, and electron microscopy. Haplotype analysis was performed to investigate the potential founder mutation.

Among the 16 patients studied, phenotypes ranged from severe muscle-eye-brain disease to milder limb-girdle muscular dystrophy. Twenty-one pathogenic variants were identified, including five novel variants. A recurrent exon 6-9 deletion emerged as the second most frequent variant (25.0%, 4/16), with haplotype analysis supporting a founder mutation in Chinese patients. At follow-up, most patients remained non-ambulatory, and one patient died of respiratory failure.

This study broadens the CRPPA mutational spectrum and identifies a founder mutation of exon 6-9 deletion in Chinese patients. These findings have important implications for population-specific screening, diagnosis, and genetic counseling.