Mutation spectrum of 260 dystrophinopathy patients from Turkey and important highlights for genetic counseling
| Autor: | Hülya Kayserili, Haluk Topaloglu, Ayaz Aghayev, Zehra Oya Uyguner, Sahin Avci, Hacer Durmus, Zuhal Yapici, Pinar Tekturk, Seher Başaran, Yesim Parman, Umut Altunoglu, Piraye Oflazer-Serdaroglu, B Sevinc Rustemoglu, Gulendam Bagirova, Feza Deymeer, Güven Toksoy, Birsen Karaman |
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| Rok vydání: | 2019 |
| Předmět: |
Adult
Male 0301 basic medicine Turkey Duchenne muscular dystrophy Genetic counseling In silico Genetic Counseling Chromosomal translocation Biology Carrier testing medicine.disease_cause Cohort Studies Dystrophin Young Adult 03 medical and health sciences 0302 clinical medicine medicine Humans Multiplex ligation-dependent probe amplification Child Genetics (clinical) Genetics Mutation High-Throughput Nucleotide Sequencing Infant Karyotype Sequence Analysis DNA medicine.disease Muscular Dystrophy Duchenne Phenotype 030104 developmental biology Neurology Child Preschool Pediatrics Perinatology and Child Health Female Neurology (clinical) 030217 neurology & neurosurgery |
| Zdroj: | Neuromuscular Disorders. 29:601-613 |
| ISSN: | 0960-8966 |
| Popis: | We genetically evaluated 260 dystrophinopathy patients from Turkey. Karyotyping as an initial test in female patients, followed stepwise by multiplex ligation-dependent probe amplification and by targeted next-generation sequencing of DMD revealed definitive genetic diagnoses in 214 patients (82%), with gross deletions/duplications in 153 (59%), pathogenic sequence variants in 60 (23%), and X-autosome translocation in one. Seven of the gross and 27 of the sequence variants found novel. In silico prediction, co-segregation and transcript assays supported the pathogenic nature of the novel silent (p.Lys534=) and the splice site (c.4345-12C>G) alterations. From a total of 189 singleton cases, 154 (82%) had pathogenic alterations. From 138 of those who had maternal carrier testing, 68 out of 103 (66%) showed gross and 11 out of 35 (31%) showed small pathogenic variants. This suggests that the de novo occurrences in DMD appear approximately 2.1 times more frequently in meiotic unequal crossing-over than in uncorrected replication errors. Our study also disclosed three mothers as obligate gonadal mosaic carriers. Family-based investigation of dystrophinopathy patients is crucial for the ascertainment of novel or rare variants and also for counseling and follow-up care of the families. |
| Databáze: | OpenAIRE |
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