RESUMO
We report on a 6-year-old child with a de novo 1.6 Mb deletion in the 3q26.31q26.32 region identified by SNP array, involving only one relevant gene: TBL1XR1. The girl shows non-specific, mild to moderate intellectual deficiency but no autistic behavior. Point mutations in TBL1XR1 have recently been implicated in three patients with intellectual disability (ID) and autistic features. Our report supports that haploinsufficiency for TBL1XR1 could be implicated in non-ASD autosomal dominant ID.
Assuntos
Deficiências do Desenvolvimento/genética , Deleção de Genes , Deficiência Intelectual/genética , Proteínas Nucleares/genética , Receptores Citoplasmáticos e Nucleares/genética , Proteínas Repressoras/genética , Criança , Pré-Escolar , Fácies , Feminino , Humanos , Recém-Nascido , Polimorfismo de Nucleotídeo Único/genética , GravidezRESUMO
Chromosome 6q duplications have been documented repeatedly, allowing the delineation of a "6q duplication syndrome," characterized by hypertelorism, downslanting palpebral fissures, tented upper lip, short neck, severe mental and growth retardation, and joint contractures. Most reported cases result from malsegregation of a reciprocal translocation leading to a terminal 6q duplication and partial monosomy of another chromosome. Only 11 cases of de novo pure duplication have been reported so far. The breakpoints do not appear to be recurrent, but in most cases they have not been characterized molecularly, precluding genotype-phenotype correlation. We report on an 8-year-old girl with a phenotype consistent with mild 6q duplication syndrome, including characteristic physical findings, mild mental retardation, and joint contractures. She carries a 13 Mb de novo 6q24.2q25.3 duplication, diagnosed by high-resolution karyotype and confirmed by array-CGH. Molecular characterization of the duplicated segment with quantitative PCR showed that the proximal breakpoint is localized within the UTRN gene, encoding utrophin, the autosomal homologue of dystrophin. We discuss the possible implication of UTRN in arthrogryposis associated with duplications spanning the 6q23q26 region.
Assuntos
Artrogripose/genética , Aberrações Cromossômicas , Cromossomos Humanos Par 6/genética , Duplicação Gênica , Utrofina/genética , Artrogripose/complicações , Pré-Escolar , Bandeamento Cromossômico , Mapeamento Cromossômico , Hibridização Genômica Comparativa , Feminino , Deformidades Congênitas da Mão/complicações , Deformidades Congênitas da Mão/diagnóstico por imagem , Humanos , Hibridização in Situ Fluorescente , Lactente , Recém-Nascido , Cariotipagem , Reação em Cadeia da Polimerase , Gravidez , RadiografiaRESUMO
We report a patient with infantile Alexander disease (AXD) due to the recurrent p.Arg79Cys GFAP mutation. In addition to typical AXD abnormalities, magnetic resonance imaging demonstrated a tumor-like lesion of the optic chiasm suggestive of a glioma. A transient papilloedema appeared during the follow-up and the lesion partially regressed despite a worsening of white matter involvement. Rare radiological and pathological tumor-like lesions have already been reported in AXD patients. This patient confirms that enlargement of the optic chiasm is a rare feature of AXD, possibly linked to abnormal astrocytic proliferation.