PT  - JOURNAL ARTICLE
AU  - Rita Selvatici
AU  - Rachele Rossi
AU  - Fernanda Fortunato
AU  - Cecilia Trabanelli
AU  - Yamina Sifi
AU  - Alice Margutti
AU  - Marcella Neri
AU  - Francesca Gualandi
AU  - Lena Szabò
AU  - Balint Fekete
AU  - Lyudmilla Angelova
AU  - Ivan Litvinenko
AU  - Ivan Ivanov
AU  - Yurtsever Vildan
AU  - Oana Alexandra Iuhas
AU  - Mihaela Vintan
AU  - Carmen Burloiu
AU  - Butnariu Lacramioara
AU  - Gabriela Visa
AU  - Diana Epure
AU  - Cristina Rusu
AU  - Daniela Vasile
AU  - Magdalena Sandu
AU  - Dmitry Vlodavets
AU  - Monica Mager
AU  - Theodore Kyriakides
AU  - Sanja Delin
AU  - Ivan Lehman
AU  - Jadranka Sekelj Fureš
AU  - Veneta Bojinova
AU  - Mariela Militaru
AU  - Velina Guergueltcheva
AU  - Birute Burnyte
AU  - Maria Judith Molnar
AU  - Niculina Butoianu
AU  - Selma Dounia Bensemmane
AU  - Samira Makri-Mokrane
AU  - Agnes Herczegfalvi
AU  - Monica Panzaru
AU  - Adela Chirita Emandi
AU  - Anna Lusakowska
AU  - Anna Potulska-Chromik
AU  - Anna Kostera-Pruszczyk
AU  - Andriy Shatillo
AU  - Djawed Bouchenak Khelladi
AU  - Oussama Dendane
AU  - Mingyan Fang
AU  - Zhiyuan Lu
AU  - Alessandra Ferlini
TI  - Ethnicity-related DMD Genotype Landscapes in European and Non-European Countries
AID  - 10.1212/NXG.0000000000000536
DP  - 2021 Feb 01
TA  - Neurology Genetics
PG  - e536
VI  - 7
IP  - 1
4099  - http://ng.neurology.org/content/7/1/e536.short
4100  - http://ng.neurology.org/content/7/1/e536.full
SO  - Neurol Genet2021 Feb 01; 7
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