Variant c.2158-2A>G in MANBA is an important and frequent cause of hereditary hearing loss and beta-mannosidosis among the Czech and Slovak Roma population- evidence for a new ethnic-specific variant

Orphanet J Rare Dis. 2020 Aug 26;15(1):222. doi: 10.1186/s13023-020-01508-3.

Abstract

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.

Keywords: Beta-mannosidosis; Ethnic-specific variant; Hearing loss; Mental retardation; Roma.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Czech Republic
  • Deafness* / genetics
  • Ethnicity
  • Hearing Loss* / genetics
  • Humans
  • Minority Groups
  • Roma* / genetics
  • Slovakia / epidemiology
  • beta-Mannosidosis*