RESUMO
Only 12 patients with a duplication of the Williams-Beuren critical region (WBCR) have been reported to date, with variable developmental, psychomotor and language delay, in the absence of marked dysmorphic features. In this paper we present a new WBCR microduplication case, which supports the wide variability displayed by this duplication in the phenotype. The WBCR microduplication may be associated with autistic spectrum disorder, but most reported cases do not show this behavioural disorder, or may even show a hypersociable personality, as with our patient. From the present case and a review of the 12 previously described, we conclude that the phenotype associated with duplication of WBCR can affect the same domains as WBCR deletion, but that they cluster near the polar ends of social relationship (autism-like v hypersociability), language (expressive language impairment v "cocktail party" speech), visuospatial (severe v normal), mental retardation (severe v mild) and dysmorphic (severe v mild) features.
RESUMO
Two novel mutations of the ribosomal S6 kinase 2 gene (also known as RSK2) have been identified in two unrelated patients with Coffin-Lowry syndrome. The first mutation consists of a de novo insertion of a 5'-truncated LINE-1 element at position -8 of intron 3, which leads to a skipping of exon 4, leading to a shift of the reading frame and a premature stop codon. The L1 fragment (2800 bp) showed a rearrangement with a small deletion, a partial inversion of the ORF 2, flanked by short direct repeats which duplicate the acceptor splice site. However, cDNA analysis of the patient shows that both sites are apparently not functional. The second family showed the nucleotide change 803T>C in exon 10, resulting in the F268S mutation. This mutation was detected in two monozygotic twin patients and in their mother, who was mildly affected. The patients fulfill the clinical criteria of the syndrome, and therefore the mutation provides further support for the importance of phenylalanine at position 268, which is highly conserved in the protein kinase domain of many serine-threonine protein kinases.
Assuntos
Síndrome de Coffin-Lowry/genética , Proteínas Quinases S6 Ribossômicas 90-kDa/genética , Adulto , Southern Blotting , Criança , Códon sem Sentido/genética , Análise Mutacional de DNA , Primers do DNA , Componentes do Gene , Humanos , Elementos Nucleotídeos Longos e Dispersos/genética , Mutação de Sentido Incorreto/genética , Linhagem , Polimorfismo Conformacional de Fita Simples , Reação em Cadeia da Polimerase Via Transcriptase Reversa , Análise de Sequência de DNARESUMO
Clinical and molecular studies are reported on a family (MRX73) of five males with non-specific X-linked mental retardation (XLMR). A total of 33 microsatellite and RFLP markers was typed. The gene for this XLMR condition was been linked to DXS1195, with a lod score of 2.36 at theta = 0. The haplotype and multipoint linkage analyses suggest localization of the MRX73 locus to an interval of 2 cM defined by markers DXS8019 and DXS365, in Xp22.2. This interval contains the gene of Coffin-Lowry syndrome (RSK2), where a missense mutation has been associated with a form of non-specific mental retardation. Therefore, a search for RSK2 mutations was performed in the MRX73 family, but no causal mutation was found. We hypothesize that another unidentified XLMR gene is located near RSK2.
