COL12A1 and Ullrich Congenital Muscular Dystrophy

COL12A1 is implicated in an autosomal recessive form of Ullrich congenital muscular dystrophy (UCMD2), presenting with hypotonia, joint hyperlaxity and frequent falls. Four probands from three unrelated families have been described: a Turkish patient homozygous for c.8903C>T (p.Pro2968Leu) (PMID:39129837), an Iranian patient homozygous for c.8828C>T (p.Pro2943Leu) (PMID:37458870), and two siblings harboring biallelic loss-of-function frameshift and nonsense variants (PMID:27348394). Segregation in two families confirms autosomal recessive inheritance with two additional affected relatives.

Functional fibroblast assays demonstrate intracellular retention of mutant COL12A1 consistent with defective collagen XII secretion and extracellular matrix disruption (PMID:27348394). No conflicting evidence has been reported. Based on limited case numbers and partial mechanistic data, this association is classified as Limited clinical validity. Key take-home: COL12A1 sequencing is warranted in patients with UCMD-like phenotypes to enable accurate diagnosis and genetic counselling.

References

• Molecular syndromology • 2024 • COL12A1 Gene Variant and a Review of the Literature: A Case Report of Ullrich Congenital Muscular Dystrophy. PMID:39129837
• Muscle & nerve • 2017 • Novel Col12A1 variant expands the clinical picture of congenital myopathies with extracellular matrix defects. PMID:27348394
• Molecular biology reports • 2023 • Whole exome sequencing identifies a novel variant in the COL12A1 gene in a family with Ullrich congenital muscular dystrophy 2. PMID:37458870

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