A novel variant in DYSF gene: A case report

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Dündar M., Aktaş Paskal Ş., Ayhan R., Baysal K., Kardaş F.

14.Ulusal Tıbbi Genetik Kongresi “Uluslararası Katılımlı”, Antalya, Turkey, 20 - 22 November 2020, pp.72

• Publication Type: Conference Paper / Summary Text
• City: Antalya
• Country: Turkey
• Page Numbers: pp.72
• Erciyes University Affiliated: Yes

Abstract

The DYSF gene is located on chromosome 2p13, which spans a genomic region of more than 230 kbp and comprises 55 exons. It encodes a transmembrane protein DYSF which has been linked to membrane repair, Ca2+ signaling, cell adhesion, and angiogenesis. Mutations in the dysferlin gene are responsible for three main dystrophic phenotypes: Limb-girdle muscular dystrophy type 2B (LGMD2B; MIM# 2536011, 2), Miyoshi myopathy (MM; MIM# 2541302) and Distal myopathy with anterior tibialis onset (DMAT; MIM# 606768.3). Here, we described a Turkish male asymptomatic patient who has incidental creatine kinase elevation in blood values (CPK:5193 U/L). He was 14 and the third child of parents who were third-degree related. We performed Next Generation Sequencing as Hereditary Disorder Solution which includes 569 protein-coding genes exons and exon-intron borders revealed a novel homozygous (c.3429 C>A (p.Tyr 1143*)) nonsense DYSF (NM_001130976) gene variant in our patient. It creates a null allele in the DYSF gene where the loss of function is a known mechanism of disease. Computational prediction tools DANN, EIGEN,FATHMM-MKL and MutationTaster (7) did pathogenic predictions for this variant and this variant has been classified as “Pathogenic” according to the ACMG 2015 guideline for interpretation of sequence variants.