title: UBE2A, which encodes a ubiquitin-conjugating enzyme, is mutated in a novel X-linked mental retardation syndrome.
abstract: We report a mutation of UBE2A/HR6A, which encodes a ubiquitin-conjugating enzyme (E2), a member of the ubiquitin proteasome pathway, as the cause of a novel X-linked mental retardation (XLMR) syndrome that affects three males in a two-generation family. A single-nucleotide substitution, c.382C-->T in UBE2A, led to a premature UAG stop codon (Q128X). As a consequence, the predicted polypeptide lacks the 25 C-terminal amino acid residues. The importance of this terminal sequence for UBE2 function is inferred by its conservation in vertebrates and in Drosophila. UBE2A mutations do not appear to significantly contribute to XLMR, since no UBE2A mutations were identified in 15 families with nonsyndromic and 4 families with syndromic idiopathic XLMR previously mapped to intervals encompassing this gene. This is the first description of a mutation in a ubiquitin-conjugating enzyme gene as the cause of a human disease.
authors.affiliation: Departamento de Genética e Biologia Evolutiva, Instituto de Biociências, Universidade de São Paulo, Caixa Postal 11461, 05422-970 São Paulo, SP, Brazil.
authors.forename: Rafaella M P
authors.initials: RM
authors.lastname: Nascimento
authors.forename: Paulo A
authors.initials: PA
authors.lastname: Otto
authors.forename: Arjan P M
authors.initials: AP
authors.lastname: de Brouwer
authors.forename: Angela M
authors.initials: AM
authors.lastname: Vianna-Morgante
mesh_terms: D000328:Adult; D000595:Amino Acid Sequence; D002675:Child, Preschool; D018389:Codon, Nonsense / Q000235:genetics; D017124:Conserved Sequence / Q000235:genetics; D004252:DNA Mutational Analysis; D006801:Humans; D008297:Male; D038901:X-Linked Intellectual Disability / Q000235:genetics*; D008875:Middle Aged; D008969:Molecular Sequence Data; D010375:Pedigree; D044763:Ubiquitin-Conjugating Enzymes / Q000235:genetics*
chemical_list: D018389:Codon, Nonsense; C471545:UBE2A protein, human; D044763:Ubiquitin-Conjugating Enzymes