RESUMEN
BACKGROUND: The vast majority of cases with Beckwith-Wiedemann syndrome (BWS) are caused by a molecular defect in the imprinted chromosome region 11p15.5. The underlying mechanisms include epimutations, uniparental disomy, copy number variations, and structural rearrangements. In addition, maternal loss-of-function mutations in CDKN1C are found. Despite growing knowledge on BWS pathogenesis, up to 20% of patients with BWS phenotype remain without molecular diagnosis. CASE PRESENTATION: Herein, we report an Iranian family with two females affected with BWS in different generations. Bisulfite pyrosequencing revealed hypermethylation of the H19/IGF2: intergenic differentially methylated region (IG DMR), also known as imprinting center 1 (IC1) and hypomethylation of the KCNQ1OT1: transcriptional start site (TSS) DMR (IC2). Array CGH demonstrated an 8 Mb duplication on chromosome 11p15.5p15.4 (205,827-8,150,933) and a 1 Mb deletion on chromosome 9p24.3 (209,020-1,288,114). Chromosome painting revealed that this duplication-deficiency in both patients is due to unbalanced segregation of a paternal reciprocal t(9;11)(p24.3;p15.4) translocation. CONCLUSIONS: This is the first report of a paternally inherited unbalanced translocation between the chromosome 9 and 11 short arms underlying familial BWS. Copy number variations involving the 11p15.5 region are detected by the consensus diagnostic algorithm. However, in complex cases which do not only affect the BWS region itself, characterization of submicroscopic chromosome rearrangements can assist to estimate the recurrence risk and possible phenotypic outcomes.
Asunto(s)
Síndrome de Beckwith-Wiedemann/genética , Padre , Linaje , Translocación Genética , Adulto , Cromosomas Humanos Par 11/genética , Inhibidor p57 de las Quinasas Dependientes de la Ciclina/genética , Femenino , Humanos , Masculino , Madres , Mutación , EmbarazoRESUMEN
Wilson's disease (WD) is a rare autosomal recessive disease due to copper metabolism disturbance. The clinical presentation spectrum of Wilson's disease is wide and initial findings of the disease depend on the organ involved. Neurologic disorders can develop insidiously or precipitously with intention tremor, dysarthria, rigid dystonia, Parkinsonism, deterioration in school performance or behavioral changes. This article is presenting an 11-yr old boy with chief complaint of falling and upper limb spasm. He referred to the Neurology Department, Ghaem Hospital, Mashhad, northeastern Iran in 2016. His symptoms began from 6 months earlier as mood instability (prolonged spontaneous crying). He was also suffering from occasionally tremor and micrographia. Initial investigations were normal and with diagnosis of depression and psychiatric problems, he had undergone treatment with fluoxetine and risperidone. Wilson's disease should be considered in the diagnosis of all children with psychiatric and musculoskeletal symptoms.
