RESUMO
A genetic linkage study was performed on a large four-generation family with variable nonspecific X-linked mental retardation (MRX16), speech abnormalities, and retardation of all milestones. Significant linkage was found in the Xq28 region with loci DXS52, DXS15, BGN, and DXS1108 with maximum LOD scores of 4.86, 4.01, 4.83, and 5.43, respectively, at theta = 0.00. Recombination was observed at the locus DXS1113, thus mapping the gene in an 8-Mb interval between this marker and the Xq telomere. Linkage intervals of three other MRX families overlap with this interval in Xq28 where the RABGDIA gene, mutated in the MRX41 and MRX48 families, is also located. In MRX3, MRX28, but also in MRX16, no alteration of RABGDIA has been found, thus suggesting the existence of at least two MRX genes in distal Xq28.
Assuntos
Ligação Genética , Deficiência Intelectual/genética , Cromossomo X , Mapeamento Cromossômico , Família , Feminino , Humanos , Cariotipagem , Escore Lod , Masculino , Testes Neuropsicológicos , Linhagem , Fenótipo , Análise de Sequência de DNARESUMO
X-linked mental retardation (XLMR) includes distinct entities in which mental deficiency is either associated with specific abnormalities (syndromal) or not (nonsyndromal). We report on the clinical, neuropsychological, and laboratory findings and linkage analysis in one family with XLMR and isolated growth hormone deficiency (IGHD). Mental retardation was associated in 3 males and 5 females with short stature, microcephaly, and particular facial traits, i.e., high curved forehead, midface hypoplasia, and concave nasal bridge with nasal end of normal size and broad traits. Significant lod scores (Zmax >2) at a recombination fraction of theta = 0 were detected for 6 marker loci between DXS178 (Xq22.1) and DXS292 (Xq27.2). This mapping region overlaps that of XLMR with IGHD, recently reported by Hamel et al. [1996: Am J Med Genet 64:35-41] (Xq24-q27.3), and that of agammaglobulinemia with IGHD (Xq21.33-q22.2). This observation may confirm the suspicion of a gene involved in growth hormone regulation being localized in Xq.
Assuntos
Ligação Genética , Hormônio do Crescimento Humano/deficiência , Deficiência Intelectual/genética , Cromossomo X , Adulto , Mapeamento Cromossômico , Mecanismo Genético de Compensação de Dose , Feminino , Humanos , Escore Lod , Masculino , Pessoa de Meia-IdadeRESUMO
Nance-Horan syndrome (NHS) is a rare X-linked condition comprising congenital cataract with microcornea, distinctive dental, and evocative facial anomalies. Intellectual handicap was mentioned in seven published NHS patients. We performed a clinical study focused on psychomotor development, intellectual abilities, and behavior in 13 affected males in four NHS families, and present the results of a neuropsychological evaluation in 7 of them. Our study confirms that mental retardation (MR) can be a major component of the NHS. Combining our data with those from the literature leads to a frequency of MR in NHS of around 30%. In most cases, MR is mild or moderate (80%) and not associated with motor delay. Conversely, a profound mental handicap associated with autistic traits may be observed. MR has intra- and inter-familial variability but does not appear to be expressed in carriers. Awareness of MR in NHS may be of importance in the management of the patients, especially in terms of education. Cloning and characterization of the gene and analysis of mutations will be an important step towards understanding the molecular basis of mental deficiency in NHS, and in delineation from the other XLMR conditions at Xp22.
Assuntos
Catarata/congênito , Catarata/genética , Ligação Genética , Deficiência Intelectual/genética , Anormalidades Dentárias/genética , Cromossomo X/genética , Anormalidades Múltiplas/genética , Adolescente , Adulto , Criança , Pré-Escolar , Córnea/anormalidades , Face/anormalidades , Feminino , Marcadores Genéticos , Humanos , Masculino , Pessoa de Meia-Idade , Testes Neuropsicológicos , Linhagem , Desempenho Psicomotor , SíndromeRESUMO
Linkage analysis was performed in a family with non-specific X-linked mental retardation (MRX 15). Hypotonia in infancy was the most remarkable physical manifestation. The severity of mental deficiency was variable among the patients, but all of them had poor or absent speech. Significant lod scores at a recombination fraction of zero were detected with the marker loci DXS1126, DXS255, and DXS573 (Zmax = 2.01) and recombination was observed with the two flanking loci DXS164 (Xp21.1) and DXS988 (Xp11.22), identifying a 17 cM interval. This result suggests a new gene localization in the proximal Xp region. In numerous families with non-specific X-linked mental retardation (MRX), the corresponding gene has been localized to the paracentromeric region in which a low recombination rate impairs the precision of mapping.
