Molecular characterization of exonic rearrangements and frame shifts in the dystrophin gene in Duchenne muscular dystrophy patients in a Saudi community.

Autor: Elhawary NA; Department of Medical Genetics, Medicine College, Umm Al-Qura University, P.O. Box 57543, Mecca, 21955, Saudi Arabia. naelhawary@uqu.edu.sa.; Department of Molecular Genetics, Faculty of Medicine, Ain Shams University, Cairo, 11566, Egypt. naelhawary@uqu.edu.sa., Jiffri EH; Department of Medical Laboratory Technology, Faculty of Applied Medical Sciences, King Abdul-Aziz University, Jeddah, Saudi Arabia., Jambi S; Department of Pediatrics, Al Hada Military Hospital, Al Hada, Saudi Arabia., Mufti AH; Department of Medical Genetics, Medicine College, Umm Al-Qura University, P.O. Box 57543, Mecca, 21955, Saudi Arabia., Dannoun A; Department of Medical Genetics, Medicine College, Umm Al-Qura University, P.O. Box 57543, Mecca, 21955, Saudi Arabia., Kordi H; Department of Medical Genetics, Medicine College, Umm Al-Qura University, P.O. Box 57543, Mecca, 21955, Saudi Arabia., Khogeer A; Department of Plan and Research, General Directorate of Health Affairs, Mecca Region, Ministry of Health, Mecca, Saudi Arabia., Jiffri OH; Department of Medical Laboratory Technology, Faculty of Applied Medical Sciences, King Abdul-Aziz University, Jeddah, Saudi Arabia., Elhawary AN; Department of Pediatrics, Faculty of Medicine, Cairo University, Giza, Egypt., Tayeb MT; Department of Medical Genetics, Medicine College, Umm Al-Qura University, P.O. Box 57543, Mecca, 21955, Saudi Arabia.
Jazyk: angličtina
Zdroj: Human genomics [Hum Genomics] 2018 Apr 10; Vol. 12 (1), pp. 18. Date of Electronic Publication: 2018 Apr 10.
DOI: 10.1186/s40246-018-0152-8
Abstrakt: Background: In individuals with Duchenne muscular dystrophy (DMD), exon skipping treatment to restore a wild-type phenotype or correct the frame shift of the mRNA transcript of the dystrophin (DMD) gene are mutation-specific. To explore the molecular characterization of DMD rearrangements and predict the reading frame, we simultaneously screened all 79 DMD gene exons of 45 unrelated male DMD patients using a multiplex ligation-dependent probe amplification (MLPA) assay for deletion/duplication patterns. Multiplex PCR was used to confirm single deletions detected by the MLPA.
Results: There was an obvious diagnostic delay, with an extremely statistically significant difference between the age at initial symptoms and the age of clinical evaluation of DMD cases (t value, 10.3; 95% confidence interval 5.95-8.80, P < 0.0001); the mean difference between the two groups was 7.4 years. Overall, we identified 147 intragenic rearrangements: 46.3% deletions and 53.7% duplications. Most of the deletions (92.5%) were between exons 44 and 56, with exon 50 being the most frequently involved (19.1%). Eight new rearrangements, including a mixed deletion/duplication and double duplications, were linked to seven cases with DMD. Of all the cases, 17.8% had duplications with no hot spots. In addition, confirmation of the reading frame hypothesis helped account for new DMD rearrangements in this study. We found that 81% of our Saudi patients would potentially benefit from exon skipping, of which 42.9% had a mutation amenable to skipping of exon 51.
Conclusions: Our study could generate considerable data on mutational rearrangements that may promote future experimental therapies in Saudi Arabia.
Databáze: MEDLINE
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