BACKGROUND: The Roma are a European ethnic minority threatened by several recessive diseases. Variants in MANBA cause a rare lysosomal storage disorder named beta-mannosidosis whose clinical manifestation includes deafness and mental retardation. Since 1986, only 23 patients with beta-mannosidosis and biallelic MANBA variants have been described worldwide. RESULTS: We now report on further 10 beta-mannosidosis patients of Roma origin from eight families in the Czech and Slovak Republics with hearing loss, mental retardation and homozygous pathogenic variants in MANBA. MANBA variant c.2158-2A>G screening among 345 anonymized normal hearing controls from Roma populations revealed a carrier/heterozygote frequency of 3.77%. This is about 925 times higher than the frequency of this variant in the gnomAD public database and classifies the c.2158-2A>G variant as a prevalent, ethnic-specific variant causing hearing loss and mental retardation in a homozygous state. The frequency of heterozygotes/carriers is similar to another pathogenic variant c.71G>A (p.W24*) in GJB2, regarded as the most frequent variant causing deafness in Roma populations. CONLCUSION: Beta-mannosidosis, due to a homozygous c.2158-2A>G MANBA variant, is an important and previously unknown cause of hearing loss and mental retardation among Central European Roma.

Department of Medical Genetics Masaryk Hospital in Usti nad Labem Regional Health Corporation Usti nad Labem Czech Republic

Department of Molecular Biology Faculty of Natural Sciences Comenius University Bratislava Slovakia

Department of Otorhinolaryngology Head and Neck Surgery Faculty of Medicine and University Hospital Comenius University Bratislava Slovakia

Diabgene Laboratory Institute of Experimental Endocrinology Biomedical Research Center Slovak Academy of Sciences Bratislava Slovakia

DNA laboratory Department of Paediatric Neurology 2nd Faculty of Medicine Charles University and Motol University Hospital Prague Czech Republic

Institute for Clinical and Translational Research Biomedical Research Center Slovak Academy of Sciences Bratislava Slovakia

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