RESUMEN
Huntington disease (HD), an autosomal dominant disorder involving HTT, is characterized by chorea, psychiatric illness and cognitive decline. Diagnosis and age of onset depend on the degree of expansion of the trinucleotide CAG repeat within the gene. The prevalence of HD is known for Europeans but has not been studied in the Israeli population. Between 2006 and 2011 we diagnosed in our adult genetics clinic ten HD probands, nine of whom were Caucasus Jews (CJ) (Azerbaijani), and one Ashkenazi Jewish. We performed haplotype analysis to look for evidence of a founder mutation, and found that of the nine CJ, eight shared the same haplotype that was compatible with the A1 haplogroup. We calculated the coalescence age of the mutation to be between 80 and 150 years. Ninety percent of our HD patients are CJ, as are 27% of the HD patients in Israel, although the CJ comprise only 1.4% of the Israeli population. Our findings suggest a higher prevalence of HD among CJ compared to the general Israeli population and are consistent with a recent founder mutation. We recommend a higher degree of suspicion for HD in CJ with subtle clinical findings.
Asunto(s)
Enfermedad de Huntington/genética , Judíos/genética , Mutación , Proteínas del Tejido Nervioso/genética , Adulto , Anciano , Alelos , Femenino , Tamización de Portadores Genéticos , Haplotipos , Humanos , Proteína Huntingtina , Israel , Masculino , Persona de Mediana Edad , Linaje , Repeticiones de Trinucleótidos , Población BlancaRESUMEN
The human WW Domain Containing Oxidoreductase (WWOX) gene was originally described as a tumor suppressor gene. However, recent reports have demonstrated its cardinal role in the pathogenesis of central nervous systems disorders such as epileptic encephalopathy, intellectual disability, and spinocerebellar ataxia. We report on six patients from three unrelated families of full or partial Yemenite Jewish ancestry exhibiting early infantile epileptic encephalopathy and profound developmental delay. Importantly, four patients demonstrated facial dysmorphism. Exome sequencing revealed that four of the patients were homozygous for a novel WWOX c.517-2A > G splice-site variant and two were compound heterozygous for this variant and a novel c.689A > C, p.Gln230Pro missense variant. Complementary DNA sequencing demonstrated that the WWOX c.517-2A > G splice-site variant causes skipping of exon six. A carrier rate of 1:177 was found among Yemenite Jews. We provide the first detailed description of patients harboring a splice-site variant in the WWOX gene and propose that the clinical synopsis of WWOX related epileptic encephalopathy should be broadened to include facial dysmorphism. The increased frequency of the c.517-2A > G splice-site variant among Yemenite Jews coupled with the severity of the phenotype makes it a candidate for inclusion in expanded preconception screening programs.
Asunto(s)
Cara/anomalías , Discapacidad Intelectual/genética , Espasmos Infantiles/genética , Proteínas Supresoras de Tumor/genética , Oxidorreductasa que Contiene Dominios WW/genética , Femenino , Estudios de Asociación Genética , Humanos , Judíos/genética , Masculino , Mutación , Linaje , YemenRESUMEN
We report the case of a 35-year-old man who presented with fever, diarrhea, and a left abdominal mass. Diagnostic studies confirmed Crohn disease and revealed an abdominal mass obstructing the left ureter with hydroureter and hydronephrosis. The patient was successfully treated conservatively, with corticosteroids and mesalamine, A review of the literature indicates a predominance of right ureteral involvement in Crohn disease, associated with a high incidence of ileocecal disease. Most of these patients were treated surgically, with resection of ileocecal lesion and/or ureterolysis. Ureteral obstruction as a complication of Crohn disease is discussed, with emphasis on conservative treatment.