Whole exome sequencing identifies a novel variant in the COL12A1 gene in a family with Ullrich congenital muscular dystrophy 2

Background: Mutations within the COL12A1 gene have been linked with the onset of congenital Ullrich muscular dystrophy 2 (UCMD2) and Bethlem myopathy. The severity of the symptoms exhibited is dependent on the mutation's type and whether it is heterozygous or homozygous.

Methods: We used whole-exome sequencing to identify disease-causing variants in a nine-year-old Iranian patient who had weakness, joint contractures, delayed motor development, and other symptoms. We confirmed the pathogenicity of the identified variant using in silico tools and verified its novelty using various databases. We also performed a co-segregation study and confirmed the presence of the variant in the patient's parents by Sanger sequencing.

Results: Our analysis identified a novel homozygous missense variant in the affected patient in COL12A1 (c.8828 C > T; p.Pro2943Leu). This is the second reported family with UCMD2 caused by a mutation in COL12A1. Our findings confirm that this mutation results in significantly more severe symptoms than Bethlem myopathy.

Conclusion: Our investigation contributes to the expanding body of evidence that links mutations in COL12A1 with UCMD2. Our findings confirm that the homozygous mutation in COL12A1 caused this condition and suggest that genetic testing for this mutation may be useful for diagnosing patients with this disease.