RESUMO
We describe a maternally transmitted genomic-imprinting syndrome of mental retardation, hypotonia, and unique dysmorphism with elongated face. We mapped the disease-associated locus to approximately 7.27 Mb on chromosome 8q24 and demonstrated that the disease is caused by a missense mutation in the maternal copy of KCNK9 within this locus. KCNK9 is maternally transmitted (imprinted with paternal silencing) and encodes K(2P)9.1, a member of the two pore-domain potassium channel (K(2P)) subfamily. The mutation fully abolishes the channel's currents--both when functioning as a homodimer or as a heterodimer with K(2P)3.1.
Assuntos
Impressão Genômica , Deficiência Intelectual/genética , Mutação , Polimorfismo Genético , Canais de Potássio de Domínios Poros em Tandem/genética , Animais , Cromossomos Humanos Par 8 , Feminino , Ligação Genética , Humanos , Masculino , Repetições de Microssatélites , Mães , Síndrome , Xenopus laevisRESUMO
Five infants of a Moslem-Arab extended family were evaluated for common and characteristic clinical findings of failure to thrive, extreme muscle weakness, severe motor delay, and moderate to severe cognitive and verbal delay. All children were below the third percentile in weight and height, and three of them had head circumference below the third percentile. Neurologic examination revealed severe hypotonia, muscle weakness, and absent deep tendon reflexes. Two children died at 2 years of age, and none of the children acquired full head control and the motor milestones of rolling and sitting. Laboratory evaluation including muscle biopsies, genetic studies, and metabolic evaluation was nondiagnostic.
Assuntos
Deficiências do Desenvolvimento/genética , Insuficiência de Crescimento/genética , Islamismo , Hipotonia Muscular/genética , Debilidade Muscular/genética , Biópsia , Deficiências do Desenvolvimento/patologia , Deficiências do Desenvolvimento/fisiopatologia , Eletroencefalografia , Potenciais Evocados , Insuficiência de Crescimento/patologia , Insuficiência de Crescimento/fisiopatologia , Saúde da Família , Feminino , Humanos , Lactente , Recém-Nascido , Imageamento por Ressonância Magnética , Masculino , Hipotonia Muscular/patologia , Hipotonia Muscular/fisiopatologia , Debilidade Muscular/patologia , Debilidade Muscular/fisiopatologia , Músculo Esquelético/patologia , Condução Nervosa , Linhagem , Espaço Subaracnóideo/diagnóstico por imagem , Espaço Subaracnóideo/patologia , UltrassonografiaRESUMO
BACKGROUND: The cause of cerebral palsy remains unknown in most cases. Factor V Leiden mutation, a common cause of hereditary thrombophilia, has been associated with CP. OBJECTIVES: To analyze the prevalence of factor V Leiden (G1691A), prothrombin (G20210A), and methylenetetrahydrofolate reductase (C677T) mutations in children with CP. METHODS: Sixty-one Jewish and Arab children with CP were studied for the presence of the three gene mutations associated with thrombophilia. RESULTS: We found that 41% of the children with CP and 33% of the controls carry one or more of the studied mutations (P = 0.348). The prevalence of the factor V mutation was 27.9% in CP and 16.4% in controls (P= 0.127). The frequency of the other two genetic factors was even less significant. The FVL mutation was found in 35% of the Arab CP patients (15/42) and in 22% of the controls from the same population (9/40) (P= 0.067). CONCLUSIONS: Each of the genetic factors studied was shown to be related to CP. Despite the high frequency of FVL among the studied patients, we were unable to prove a significant correlation between FVL and CP, mainly because this factor is frequent in the Arab control group. In this population a trend toward significance can be seen (P= 0.067). Larger studies are needed to validate the significance of these results.
Assuntos
Paralisia Cerebral/genética , Fator V/genética , Trombofilia/genética , Adolescente , Árabes , Estudos de Casos e Controles , Paralisia Cerebral/etiologia , Criança , Pré-Escolar , Feminino , Humanos , Lactente , Israel , Judeus , Masculino , Metilenotetra-Hidrofolato Desidrogenase (NADP)/genética , Protrombina/genética , Fatores de Risco , Trombofilia/complicaçõesRESUMO
The clinical diagnosis of ASS (Aarskog-Scott syndrome or Faciogenital Dysplasia) was made in seven individuals belonging to a large Arabic family, which was supported by molecular studies revealing a 2189delA mutation in exon 15 of the FDG1 gene. The affected individuals in this family demonstrated clinical variability particularly in their cognitive skills, raising the question whether other genetic factors might be involved in the phenotypic evolution of ASS.