Mutations in COL6A Gene Family Responsible for Muscular Dystrophies in Three Unrelated Families

Authors
Nasibeh Soltani 1
Zahra Shahbazi 1
Morteza Karimipoor 2
Mohammad Sadegh Fallah 3
Fatemeh Zafarghandi Motlagh 3
Masoume Amini 3
Mojdeh Jamali 3
Hamideh Bagherian 3
Razie Zeinali 3
Sirous Zeinali 3
1 Department of Molecular Medicine, Biotechnology Research Center, Pasteur Institute of Iran, Tehran, Iran
2 1Department of Molecular Medicine, Biotechnology Research Center, Pasteur Institute of Iran, Tehran, Iran
3 Department of Human Genetics, Kawsar Human Genetics Research Center, Tehran, Iran
10.61186/ibj.4018
Abstract
Background: Muscular dystrophy is an inherited disease with clinical and genetic heterogeneity. Muscle weakness is the primary symptom of these disorders that often leads to disability and death. The overall prevalence for all types of muscular dystrophies worldwide is 19.8-25.1 per 100.000 population. Autosomal recessive types of muscular dystrophies are more common in Iran, likely due to the high rate of consanguineous marriage. We aimed at deciphering molecular defects in three unrelated families with muscular dystrophies not related to Duchene muscular dystrophy (MD) or limb girdle muscular dystrophies. We are reporting families having affected children with MD owing to the mutations in three genes related to the COL6A (collagen type VI, alpha subunit) gene family.

Methods: Three unrelated families, who had at least one member affected with MD and for whom a definite molecular diagnosis was not provided by routine methods, were investigated by WES and confirmed by Sanger sequencing.

Results: In the first family, a homozygous variant was found in the COL6A3 gene (NM_004369.4:c.4390C>T:p.Arg1464Ter), which explains the clinical symptoms observed in this family. In the second family, two homozygote missense variants with possible relevance to the patient’s phenotype were identified in COL6A1 and COL6A2 genes (NM_001848.2:c.803A>G: p.Glu268Gly and NM_001849.3:c.2489G>A:p.Arg830Gln). Also, a heterozygous pathogenic variant in the COL6A2 gene (NM_001849.3: c.1053+1G>T) was detected in the third family.

Conclusion: WES can serve as an effective method for detecting the causative mutations in families with unresolved cases of MD. The data provided herein broadens the spectrum of mutations causing MD in Iran.
Keywords
Collagen Type VI
Exome sequencing
Muscular dystrophies
Iranian Biomedical Journal
Volume 28, Issue 5 - Serial Number 115
September and October 2024
Pages 297-304