Identification of a novel mutation in col6a2 gene in a patient with ullrich congenital muscular dystrophy

Aziz Khorrami,1 Shahin behrouz sharif,2 Saba dayem omid,3 Mahan narjabadifam,4 Seyyed vahid mohaddes ardebili,5 Seyyed mojtaba mohaddes ardebili,6,*

1. Department of Genetics, Faculty of Natural Sciences, University of Tabriz
2. Department of Human Genetics, Faculty of Medicine, Tabriz University of Medical Sciences
3. Drug Applied Research Center, Tabriz University of Medical Sciences
4. Department of Genetics, Faculty of Natural Sciences, University of Tabriz
5. Department of Genetics, Faculty of Natural Sciences, University of Tabriz
6. Department of Human Genetics, Faculty of Medicine, Tabriz University of Medical Sciences

Abstract

Introduction

Ullrich congenital muscular dystrophy is a progressive condition with typically autosomal recessive inheritance pattern that mainly affects skeletal muscles. severe muscle weakness soon after birth, developing contractures in knees and elbows, and hypermobility in wrists and ankles are main manifestations. most patients are unable to walk or walk for only a short period of time, usually before puberty. mutations in the col6a1, col6a2, and col6a3 genes have been reported as underlying causes. here in we report a case with a new pathogenic mutation in col6a2.

Methods

A 7-year-old symptomatic female result of a consanguineous marriage of first cousin parents with muscular weakness and possible diagnosis of hereditary muscular disease, due to the positive history of similar conditions in her cousins, was subjected to next generation sequencing. detected variations were then validated using targeted sanger sequencing. the initial investigation for suspected smn1 gene defects was negative.

Results

One homozygote mutation (c.714+2t>c) on col6a2 gene has been detected although it has not been reported previously. heterozygous and homozygous statuses for this mutation were also validated in parents and affected individuals, respectively.

Conclusion

C.714+2t>c point mutation alters the splice donor site of intron 3 in col6a2 gene with possible contribution to aberrant splicing and ultimately defected protein. this unprecedentedly reported mutation on col6a2 gene has pathogenic effects which seems to culminate directly with ullrich congenital muscular dystrophy.

Keywords

Ullrich congenital muscular dystrophy, col6a2, c.714+2t>c