Mutational Spectrum of DMD Gene Variants and Cascade Screening Outcomes in the Central-Eastern Black Sea Region of Türkiye: A Single-Centre Retrospective Study.

BACKGROUND: Duchenne and Becker muscular dystrophies arise from pathogenic variants in the DMD gene at Xp21.2. Their spectrum is uncharacterised in the Central-Eastern Black Sea region of Türkiye. METHODS: We reviewed all consecutive individuals tested for DMD variants at our centre from January 2022 to February 2026. Multiplex ligation-dependent probe amplification was available in 45 of 47 and whole-gene sequencing in 16, run in parallel in 13. Variants were described against NM_004006.3 (LRG_199t1) and classified per the 2015 ACMG/AMP and 2020 ACMG/ClinGen copy-number standards. RESULTS: Among 47 individuals (29 female, 18 male; median age 12.8 years, IQR 1.3-36.7), pathogenic variants were found in 19: ten probands and nine cascade-detected heterozygotes. Diagnostic yield in index testing was 30.3% (10/33; 95% CI 17.4-47.3%) and the cascade carrier-detection rate 64.3% (9/14; 95% CI 38.8-83.7%). Seven deletions and two sequence variants (NM_004006.3:c.701 C > G p.(Ser234Ter); c.2803 + 1G > T) were identified, six of nine families carrying distal-hotspot deletions (exons 45-55). Three deletions were in-frame and four out-of-frame, verified in LOVD and DOVE. Four heterozygotes, three of them probands, had unexplained hyperCKemia (776-2,816 U/L) without documented weakness; the one fully assessed had normal strength and echocardiogram. Two deletions were apparently de novo, and no proband was amenable to an approved exon-skipping oligonucleotide. CONCLUSION: The DMD variant spectrum in this first regional series was broadly congruent with national and global patterns, and cascade screening identified nine further heterozygotes. Given the small number of probands, these proportions are descriptive rather than prevalence estimates, and genotype-based phenotype assignment requires prospective confirmation.