RT Journal Article
SR Electronic
T1 Novel duplication mutation of the DYSF gene in a Pakistani family with Miyoshi Myopathy
JF Saudi Medical Journal
JO Saudi Med J
FD Prince Sultan Military Medical City
SP 1190
OP 1195
DO 10.15537/smj.2017.12.20989
VO 38
IS 12
A1 Ullah, Muhammad I.
A1 Ahmad, Arsalan
A1 Žarković, Milena
A1 Shah, Syed S.
A1 Nasir, Abdul
A1 Mahmood, Saqib
A1 Ahmad, Wasim
A1 Hübner, Christian A.
A1 Hassan, Muhammad J.
YR 2017
UL http://smj.org.sa/content/38/12/1190.abstract
AB Objectives: To identify the underlying gene mutation in a large consanguineous Pakistani family.Methods: This is an observational descriptive study carried out at the Department of Biochemistry, Shifa International Hospital, Quaid-i-Azam University, and Atta-ur-Rahman School of Applied Biosciences, National University of Sciences and Technology, Islamabad, Pakistan from 2013-2016. Genomic DNA of all recruited family members was extracted and the Trusight one sequencing panel was used to assess genes associated with a neuro-muscular phenotype. Comparative modeling of mutated and wild-type protein was carried out by PyMOL tool.Results: Clinical investigations of an affected individual showed typical features of Miyoshi myopathy (MM) like elevated serum creatine kinase (CK) levels, distal muscle weakness, myopathic changes in electromyography (EMG) and muscle histopathology. Sequencing with the Ilumina Trusight one sequencing panel revealed a novel 22 nucleotide duplication (CTTCAACTTGTTTGACTCTCCT) in the DYSF gene (NM_001130987.1_c.897-918dup; p.Gly307Leufs5X), which results in a truncating frameshift mutation and perfectly segregated with the disease in this family. Protein modeling studies suggested a disruption in spatial configuration of the putative mutant protein.Conclusion: A novel duplication of 22 bases (c.897_918dup; p.Gly307Leufs5X) in the DYSF gene was identified in a family suffering from Miyoshi myopathy. Protein homology analysis proposes a disruptive impact of this mutation on protein function.