Abstract
BackgroundThe 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.ResultsWe 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.ConlcusionBeta-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.
Highlights
The Roma are a European ethnic minority threatened by several recessive diseases
If we try to trace the origin of the MANBA variant, we have to consider the following facts: our findings show the variant c.2158-2A>G to be an important cause of hearing loss in the Czech and Slovak Roma, but not in non-Roma European populations
The detected c.2158-2A>G variant in MANBA is another important ethnic-specific variant threatening the Roma population in Central Europe
Summary
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. The clinical manifestation varies between mild and severe, involving symptoms such as mental retardation, hyperactivity, behavioural problems, hearing loss, and frequent infections of the skin and respiratory tract. The girl suffered from severe psychomotor retardation, bone deformities, face dysmorphology - gargoylism, recurrent skin and respiratory infections and died due to bronchopneumonia and sepsis aged 20. The symptoms of her brother were milder but he presented with gargoyle facial dysmorphology, mental retardation, hearing impairment and recurrent infections
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