Mutation spectrum of 260 dystrophinopathy patients from Turkey and important highlights for genetic counseling

Toksoy, Güven; Durmuş, Hacer; Aghayev, Agharza; Багирова, Г. Г.; Rustemoglu, B Sevinc; Başaran, Seher; Avcı, Şahin; Karaman, Birsen; Parman, Yeşim; Altunoğlu, Umut; Yapıcı, Zühal; Tektürk, Pınar; Deymeer, Feza; Topaloǧlu, Haluk; Kayserili, Hülya; Oflazer-Serdaroğlu, P.; Uyguner, Zehra Oya

doi:10.1016/j.nmd.2019.03.012

Cited by 18 publications

(6 citation statements)

References 44 publications

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“…According to Elhavary et al 2019, the higher percentage of deletions observed in Turkey compared to Saudi Arabia may be attributed to the admixture of Turkish populations with those of European descent [ 58 ]. However, a study conducted by Toksoy et al 2019 on Turkish patients with DMD report a deletion percentage of 48.8%, which is similar to the percentage observed in the Saudi community [ 62 ]. Therefore, it is crucial to conduct further investigations on the hypothesis that European admixture results in higher deletion percentages.…”

Section: Discussionmentioning

confidence: 58%

Title-molecular diagnostics of dystrophinopathies in Sri Lanka towards phenotype predictions: an insight from a South Asian resource limited setting

Wijekoon,

Gonawala,

Ratnayake

et al. 2024

Eur J Med Res

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Background The phenotype of Duchenne muscular dystrophy (DMD) and Becker muscular dystrophy (BMD) patients is determined by the type of DMD gene variation, its location, effect on reading frame, and its size. The primary objective of this investigation was to determine the frequency and distribution of DMD gene variants (deletions/duplications) in Sri Lanka through the utilization of a combined approach involving multiplex polymerase chain reaction (mPCR) followed by Multiplex Ligation Dependent Probe Amplification (MLPA) and compare to the international literature. The current consensus is that MLPA is a labor efficient yet expensive technique for identifying deletions and duplications in the DMD gene. Methodology Genetic analysis was performed in a cohort of 236 clinically suspected pediatric and adult myopathy patients in Sri Lanka, using mPCR and MLPA. A comparative analysis was conducted between our findings and literature data. Results In the entire patient cohort (n = 236), mPCR solely was able to identify deletions in the DMD gene in 131/236 patients (DMD-120, BMD-11). In the same cohort, MLPA confirmed deletions in 149/236 patients [DMD-138, BMD -11]. These findings suggest that mPCR has a detection rate of 95% (131/138) among all patients who received a diagnosis. The distal and proximal deletion hotspots for DMD were exons 45–55 and 6–15. Exon 45–60 identified as a novel in-frame variation hotspot. Exon 45–59 was a hotspot for BMD deletions. Comparisons with the international literature show significant variations observed in deletion and duplication frequencies in DMD gene across different populations. Conclusion DMD gene deletions and duplications are concentrated in exons 45–55 and 2–20 respectively, which match global variation hotspots. Disparities in deletion and duplication frequencies were observed when comparing our data to other Asian and Western populations. Identified a 95% deletion detection rate for mPCR, making it a viable initial molecular diagnostic approach for low-resource countries where MLPA could be used to evaluate negative mPCR cases and cases with ambiguous mutation borders. Our findings may have important implications in the early identification of DMD with limited resources in Sri Lanka and to develop tailored molecular diagnostic algorithms that are regional and population specific and easily implemented in resource limited settings.

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Section: Discussionmentioning

confidence: 58%

Title-molecular diagnostics of dystrophinopathies in Sri Lanka towards phenotype predictions: an insight from a South Asian resource limited setting

Wijekoon,

Gonawala,

Ratnayake

et al. 2024

Eur J Med Res

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“…Frameshift was the second most prevalent type of point variant. It was identified in 18 patients (31%), nearly at the same prevalence rate reported in China (28.29%) and Eastern Europe (29%), and at a higher prevalence rate than in the Turkish target population (6%) [ [24] , [25] , [26] ]. Micro deletion and insertion altered the open reading frame and caused early termination of the amino acid coding, which can lead to the production of truncated dystrophin protein, typically associated with the DMD phenotype.…”

Section: Discussionmentioning

confidence: 64%

Next-generation sequencing approach to molecular diagnosis of Iranian patients with Duchenne/Becker muscular dystrophy: Several novel variants identified

Bakhshandeh¹,

Behroozi²,

Ghorbani³

2023

eNeurologicalSci

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“…This result is consistent with the report of Zimowski et al (5) in a Polish population, in which the carrier frequency was 61.9% for DMD and 68.1% for BMD. A report by Toksoy et al (13) in a Turkish population also revealed no statistically significant difference between the carrier frequency of DMD and BMD, with 45.5% for DMD and 42.9% for BMD. In contrast, Lee et al (11) reported a significant difference in the carrier frequencies of DMD (57.6%) and BMD (89.5%) in a Japanese population, probably due to the small number of tested mothers (Table 3).…”

Section: Discussionmentioning

confidence: 80%

Comparison of Carrier and de novo Pathogenic Variants in a Chinese DMD/BMD Cohort

Lin

Liao

et al. 2021

Front. Neurol.

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Background: Duchenne and Becker muscular dystrophy (DMD/BMD) are X-linked recessively inherited neuromuscular disorders caused by deletions, duplications, or small mutations in the DMD gene. With advances in prenatal diagnosis decreasing the number of affected offspring from carrier mothers, the frequency of de novo variants could increase. Therefore, determining the differences between the carrier and de novo variants of the DMD gene, which are rarely explored, is important for trial planning and genetic diagnosis in the future.Methods: A total of 440 patients, 349 of whom had DMD and 91 had BMD, diagnosed in our department between 2012 and 2019, along with their respective mothers, were included in this study. Multiplex ligation-dependent probe amplification was used to detected deletions and duplications in patients and their mothers. Small mutations were detected using next-generation sequencing in the patients, followed by Sanger sequencing in the mothers.Results: Deletions, duplications, and small mutations were identified in 204, 46, and 99 of the 349 patients with DMD and in 50, 10, and 31 of the 91 patients with BMD, respectively. De novo deletions were more concentrated in hotspot regions than carrier deletions of DMD/BMD. No clear bias was observed in the variant distribution between carriers, de novo duplications, and small mutations in DMD/BMD. The carrier frequency of DMD (61.6%) was lower than that of BMD (69.2%), but the difference was not statistically significant. The carrier frequency of deletions of the DMD gene (51.2%) was significantly lower than those of duplications (75%) and small mutations (81.5%).Conclusion: Compared to de novo deletions, deletions from carrier mothers had a wider distribution. Moreover, there was no significant difference between the carrier frequencies of DMD and BMD. Duplications and small mutations were more commonly inherited, while deletions were present de novo.

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Mutation spectrum of 260 dystrophinopathy patients from Turkey and important highlights for genetic counseling

Cited by 18 publications

References 44 publications

Title-molecular diagnostics of dystrophinopathies in Sri Lanka towards phenotype predictions: an insight from a South Asian resource limited setting

Title-molecular diagnostics of dystrophinopathies in Sri Lanka towards phenotype predictions: an insight from a South Asian resource limited setting

Next-generation sequencing approach to molecular diagnosis of Iranian patients with Duchenne/Becker muscular dystrophy: Several novel variants identified

Comparison of Carrier and de novo Pathogenic Variants in a Chinese DMD/BMD Cohort

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