UCMD and BM are characterized by muscle weakness that represents the opposite end of ColVI related myopathy from BM with static course to UCMD with severe course observed by Electromyography (EMG) .
Till this point in time, no treatment has been introduced to COL6A related muscular dystrophy, the symptoms are just managed as we cited before. Recent research in the mice model of collagen typeVI deficiency (Col6α1−/−) shows that CyclosporineA can revive at least part of affected tissue caused by mitochondrial deficiency .
Collagen typeVI deficiency is caused by a stop codon at the genome or frameshift including insertion, deletion, duplication, and splice changes, which could lead to mitochondrial defect (mitochondrial abnormality spanning from tubular cristae to electron-dense matrix with alteration of threshold voltage for PTP opening caused by F1F0-ATPase Inhibitor oligomycin), sarcoplasmic reticulum, decreased autophagy (a crucial reaction against muscle wasting), impaired muscle regeneration, and variation in fiber size atrophy, which are mostly replaced by fibrotic tissue in the diaphragm, and finally ending in maturation deficiency [8, 9].
Besides, in 80 to 99% of symptoms that follow these alterations are due to muscle weakness in all four limbs that could result in limited or loose mobility before adulthood.
And by according to in terms of MRI findings, collagen typeVI related to myopathy is characterized by fatty Infiltration, contracture of spine, hyperlaxity of distal joints (finger, wrist, toes), and hyperlaxity of axial and proximal joints (hips, shoulder, knees). This sign was observed in two brothers in upper and lower limb extremities caused by pathogenic variant in exon25, NM_001848:c.1667G > T;NP_001839.2:p.Gly556Val [10, 11].
Reduction in paxillin and PI3K signaling, owing to reduced activation of CDC42 when mutations occur in collagen typeVI leads to respiratory failure, bronchopneunemonia, and diaphragmatic paresis and is a common cause of death at the first or second decade of life .
Changes in skin by follicular keloids or atrophic scar formation (keratosis pilaris associated with atopy its common skin condition in ColVI deficiency) , are associated with hypotonia at birth and tight chilies tendon. Mutation (c.227 + 2 T > C) in the COL6A1 gene causes torticholis, cervical, and lumbar spine rigidity, which may be due to asymmetric contracture in mm. scalenii, and m. sternocleidomastoideus .
In contrast to previous studies, the most complications in our proband were in trunk and pelvic girdle and didn’t show any involvement in PNS leading to spinal cord, or any symptoms in skin that was mentioned in the previous study.
Hence, in this study, we reported a 4-year-old boy with a pathogenic mutation in COL6α1 related myopathy. We initially focused on the analysis of the UCMD proband who exposed a compound homozygosis for autosomal recessive COL6α1 mutation. A deletion within exon35 NM_001848.3:c.2551_2562del:p.Phe851_Arg854 eliminated 12 bp. Genetic testing was performed through whole-exome sequencing (WES).
WES and PCR analysis for the UCMD patient revealed pathogenicity of novel mutation categorized in developmental delay motor. The pattern of inheritance is autosomal recessive because the patient carried the homozygous mutation and his parents were heterozygous for the detected mutation.