Abstract
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.
Funder
Agentura Pro Zdravotnický Výzkum České Republiky
Ministerstvo Zdravotnictví Ceské Republiky
Agentúra na Podporu Výskumu a Vývoja
Grantová Agentura, Univerzita Karlova
Publisher
Springer Science and Business Media LLC
Subject
Pharmacology (medical),Genetics(clinical),General Medicine
Reference41 articles.
1. Wenger DA, Sujansky E, Fennessey PV, Thompson JN. Human beta-mannosidase deficiency. N Engl J Med. 1986;315(19):1201–5.
2. Cooper A, Sardharwalla IB, Roberts MM. Human beta-mannosidase deficiency. N Engl J Med. 1986;315(19):1231.
3. Cooper A, Wraith JE, Savage WJ, Thornley M, Noronha MJ. Beta-mannosidase deficiency in a female infant with epileptic encephalopathy. J Inherit Metab Dis. 1991;14(1):18–22.
4. Dorland L, Duran M, Hoefnagels FE, Breg JN, Fabery de Jonge H, Cransberg K, et al. Beta-mannosidosis in two brothers with hearing loss. J Inherit Metab Dis. 1988;11(Suppl 2):255–8.
5. Kleijer WJ, Hu P, Thoomes R, Boer M, Huijmans JG, Blom W, et al. Beta-mannosidase deficiency: heterogeneous manifestation in the first female patient and her brother. J Inherit Metab Dis. 1990;13(6):867–72.
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