RESUMEN
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
Although antibiotic-resistant pneumococci have been frequently detected among day care center (DCC) attendees, the transmission of these organisms to other members of the community has not been adequately studied. Nasopharyngeal cultures were obtained from 152 children and 244 adult members of a closed community (a kibbutz) in Israel. Serotyping, antibiogram, and pulsed-field gel electrophoresis were performed to determine the relatedness of isolated pneumococci. Twenty (30%) of the 66 isolates from children showed decreased susceptibility to penicillin and 9 isolates (14%) were resistant to > or =3 drugs. Of the 16 isolates from adults, 5 (31%) were intermediately resistant to trimethoprim-sulfamethoxazole. Resistant strains carried by DCC attendees were not isolated either from their parents or from other adult members of the community. Despite the high degree of interpersonal contact occurring in a closed community, resistant pneumococcal strains carried by DCC attendees do not appear to be easily transmitted to the adult population, which suggests the existence of an immunological barrier.
