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Novel missense mutations in the ubiquitination‐related gene UBE2A cause a recognizable X‐linked mental retardation syndrome
Author(s) -
Budny B,
BaduraStronka M,
MaternaKiryluk A,
Tzschach A,
Raynaud M,
LatosBielenska A,
Ropers HH
Publication year - 2010
Publication title -
clinical genetics
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.543
H-Index - 102
eISSN - 1399-0004
pISSN - 0009-9163
DOI - 10.1111/j.1399-0004.2010.01429.x
Subject(s) - missense mutation , genetics , biology , mutation , gene , genetic linkage , phenotype
Budny B, Badura‐Stronka M, Materna‐Kiryluk A, Tzschach A, Raynaud M, Latos‐Bielenska A, Ropers HH. Novel missense mutations in the ubiquitination‐related gene UBE2A cause a recognizable X‐linked mental retardation syndrome. Recently, a truncating mutation of the UBE2A gene has been observed in a family with X‐linked mental retardation (XLMR) (1). The three affected males had similar phenotypes, including seizures, obesity, marked hirsutism and a characteristic facial appearance. Here, we report on two families with a total of seven patients and a clinically very similar syndromic form of XLMR. Linkage analysis was performed in the larger of these families, and screening several positional candidate genes revealed a G23R missense mutation in the UBE2A gene. Subsequent UBE2A screening of a phenotypically similar second family revealed another missense mutation, R11Q, again affecting an evolutionarily conserved amino acid close to the N‐terminus of the protein. SIFT and PolyPhen analyses suggest that both mutations are pathogenic, which is supported by their absence in 168 healthy controls. Thus, both missense and truncating mutations can give rise to a specific, syndromic form of XLMR which is identifiable in a clinical setting.