RT Journal Article
SR Electronic
T1 Ethnicity-related DMD Genotype Landscapes in European and Non-European Countries
JF Neurology Genetics
JO Neurol Genet
FD Lippincott Williams & Wilkins
SP e536
DO 10.1212/NXG.0000000000000536
VO 7
IS 1
A1 Rita Selvatici
A1 Rachele Rossi
A1 Fernanda Fortunato
A1 Cecilia Trabanelli
A1 Yamina Sifi
A1 Alice Margutti
A1 Marcella Neri
A1 Francesca Gualandi
A1 Lena Szabò
A1 Balint Fekete
A1 Lyudmilla Angelova
A1 Ivan Litvinenko
A1 Ivan Ivanov
A1 Yurtsever Vildan
A1 Oana Alexandra Iuhas
A1 Mihaela Vintan
A1 Carmen Burloiu
A1 Butnariu Lacramioara
A1 Gabriela Visa
A1 Diana Epure
A1 Cristina Rusu
A1 Daniela Vasile
A1 Magdalena Sandu
A1 Dmitry Vlodavets
A1 Monica Mager
A1 Theodore Kyriakides
A1 Sanja Delin
A1 Ivan Lehman
A1 Jadranka Sekelj Fureš
A1 Veneta Bojinova
A1 Mariela Militaru
A1 Velina Guergueltcheva
A1 Birute Burnyte
A1 Maria Judith Molnar
A1 Niculina Butoianu
A1 Selma Dounia Bensemmane
A1 Samira Makri-Mokrane
A1 Agnes Herczegfalvi
A1 Monica Panzaru
A1 Adela Chirita Emandi
A1 Anna Lusakowska
A1 Anna Potulska-Chromik
A1 Anna Kostera-Pruszczyk
A1 Andriy Shatillo
A1 Djawed Bouchenak Khelladi
A1 Oussama Dendane
A1 Mingyan Fang
A1 Zhiyuan Lu
A1 Alessandra Ferlini
YR 2021
UL http://ng.neurology.org/content/7/1/e536.abstract
AB Objective Genetic diagnosis and mutation identification are now compulsory for Duchenne (DMD) and Becker muscular dystrophies (BMD), which are due to dystrophin (DMD) gene mutations, either for disease prevention or personalized therapies. To evaluate the ethnic-related genetic assortments of DMD mutations, which may impact on DMD genetic diagnosis pipelines, we studied 328 patients with DMD and BMD from non-European countries.Methods We performed a full DMD mutation detection in 328 patients from 10 Eastern European countries (Poland, Hungary, Lithuania, Romania, Serbia, Croatia, Bosnia, Bulgaria, Ukraine, and Russia) and 2 non-European countries (Cyprus and Algeria). We used both conventional methods (multiplex ligation-dependent probe amplification [MLPA] followed by gene-specific sequencing) and whole-exome sequencing (WES) as a pivotal study ran in 28 patients where DMD mutations were already identified by standard techniques. WES output was also interrogated for DMD gene modifiers.Results We identified DMD gene mutations in 222 male patients. We identified a remarkable allele heterogeneity among different populations with a mutation landscape often country specific. We also showed that WES is effective for picking up all DMD deletions and small mutations and its adoption could allow a detection rate close to 90% of all occurring mutations. Gene modifiers haplotypes were identified with some ethnic-specific configurations.Conclusions Our data provide unreported mutation landscapes in different countries, suggesting that ethnicity may orient genetic diagnosis flowchart, which can be adjusted depending on the mutation type frequency, with impact in drug eligibility.ACMG=American College of Medical Genetics and Genomics; BMD=Becker muscular dystrophy; CK=creatine kinase; DMD=Duchenne muscular dystrophy; IGV=Integrative Genomics Viewer; LGMD=limb-girdle muscular dystrophy; NGS=next-generation sequencing; OMIM=Online Mendelian Inheritance in Man; VUS=variant of uncertain/unknown significance; WES=whole-exome sequencing; WGS=whole-genome sequencing