ObjectiveGenetic 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.MethodsWe 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.ResultsWe 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.ConclusionsOur 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.

Vanishing White Matter Disease (VWMD), also known as Childhood Ataxia with Central Hypomyelination (CACH) is a leukoencephalopathy with an autosomal recessive inheritance. It is caused by mutations in any of the fi ve genes encoding the fi ve subunits of the eukaryotic translational initiation factor 2B (eIF2B). Although VWMD was initially described in young children, it is now well known that it has a wide phenotypic spectrum, affecting people of all ages.VWMD is typically characterized by normal or mildly delayed initial psychomotor development, followed by episodic or chronic neurological deterioration, often provoked by infections or minor head trauma. Neurological signs consist mainly of cerebellar ataxia and spasticity. There is no specifi c treatment beside the "prevention" of cellular stress. Therefore, early recognition of the diagnosis is important to avoid triggering factors and allow genetic counseling.The reported case describes the clinical and radiological characteristics of a patient with adulthood onset of VWMD, revealed by subcortical dementia.

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