RESUMO
Beckwith Wiedemann Syndrome (BWS, OMIM 130650) is an imprinting disorder that may present antenatally with a constellation of sonographic features namely polyhydramnios, macrosomia, macroglossia, omphalocele, placental mesenchymal dysplasia, cardiomegaly, nephromegaly, fetal hydrops, and other rare anomalies. Paternal uniparental disomy in chromosome 11p15 imprinting region accounts for 20% of all BWS, and 8% among those were due to genome-wide paternal uniparental disomy (GWpUPD). GWpUPD is a rare condition and usually results in prenatal lethality. The 31 liveborns reported in the literature demonstrate female predominance in surviving GWpUPD. Here, we reported two prenatal cases which initially presented with features suggestive of BWS, which subsequently were confirmed to have GWpUPD. Further trio SNP genotyping analysis using SNP-based chromosomal microarray revealed androgenetic biparental chimera as the underlying cause. Finally, we highlighted the importance of recognizing GWpUPD as a possible cause in a fetus presenting with BWS phenotype, as it carried a different disease prognosis, tumor predisposition, manifestations of other imprinting disorders, and possibility in unmasking autosomal recessive disorders from the paternal alleles.
Assuntos
Síndrome de Beckwith-Wiedemann , Androgênios , Síndrome de Beckwith-Wiedemann/diagnóstico , Síndrome de Beckwith-Wiedemann/genética , Quimera , Metilação de DNA/genética , Feminino , Feto , Impressão Genômica/genética , Humanos , Placenta , Gravidez , Dissomia Uniparental/genéticaRESUMO
Rubinstein-Taybi syndrome (RSTS, OMIM*180849) is a rare autosomal dominant disorder, characterized by distinctive facial features, short stature, broad and often angulated thumbs and halluces, with occasional congenital anomalies. Characteristic facial dysmorphic features include downslanting palpebral fissures, low hanging columella. RSTS is caused by pathogenic variants in two ubiquitously expressed and highly homologous genes, CREBBP (OMIM*600140) and EP300 (OMIM*600140). Clinical features were well reported especially in Caucasian ethnicity. We would like to report the clinical phenotype of RSTS in our Chinese population and highlight four novel mutations in CREBBP gene.
Assuntos
Proteína de Ligação a CREB/genética , Proteína p300 Associada a E1A/genética , Predisposição Genética para Doença , Síndrome de Rubinstein-Taybi/genética , Adolescente , Adulto , Criança , Pré-Escolar , China/epidemiologia , Feminino , Mutação da Fase de Leitura/genética , Humanos , Lactente , Masculino , Pessoa de Meia-Idade , Mutação de Sentido Incorreto/genética , Fenótipo , Síndrome de Rubinstein-Taybi/epidemiologia , Síndrome de Rubinstein-Taybi/patologia , Adulto JovemRESUMO
Mandibular hypoplasia, deafness, progeroid feature, and lipodystrophy syndrome (MDPL, MIM# 615381) is an extremely rare and recently recognized early adult onset of progeroid syndrome, with features of generalized lipodystrophy, dysmorphic features, telangiectasia, early onset hearing loss, insulin resistance, and dyslipidemia. Here, we present a 31-year-old Chinese woman with MDPL, harboring the recurrent pathogenic variant p.(Ser605del) in POLD1, illustrating the evolving manifestations of this premature aging disorder from infancy to adulthood.
Assuntos
Anormalidades Múltiplas/genética , DNA Polimerase III/genética , Lipodistrofia Generalizada Congênita/genética , Micrognatismo/genética , Progéria/genética , Adulto , DNA Polimerase III/deficiência , Surdez/genética , Progressão da Doença , Dislipidemias/genética , Feminino , Genes Dominantes , Humanos , Resistência à Insulina/genética , Miopia/genética , Síndrome , Telangiectasia/genética , Magreza/genéticaRESUMO
BACKGROUND: Rotavirus is a common infectious cause of childhood hospitalisation in Hong Kong. Rotavirus vaccines have been used in the private sector since licensure in 2006 but have not been incorporated in the government's universal Childhood Immunisation Programme. This study aimed to evaluate rotavirus vaccine effectiveness against hospitalisation. METHODS: This case-control study was conducted in the 2014/2015 rotavirus season in six public hospitals. Hospitalised acute gastroenteritis patients meeting inclusion criteria were recruited and copies of their immunisation records were collected. Case-patients were defined as enrolled subjects with stool specimens obtained in the first 48h of hospitalisation that tested positive for rotavirus, whereas control-patients were those with stool specimens obtained in the first 48h of hospitalisation testing negative for rotavirus. Vaccine effectiveness for administration of at least one dose of either Rotarix(®) (GlaxoSmithKline Biologicals) or RotaTeq(®) (Merck Research Laboratories) was calculated as 1 minus the odds ratio for rotavirus vaccination history for case-patients versus control-patients. RESULTS: Among the 525 eligible subjects recruited, immunisation records were seen in 404 (77%) subjects. 31% (162/525 and 126/404) tested positive for rotavirus. In the 404 subjects assessed for vaccine effectiveness, 2.4% and 24% received at least 1 dose of either rotavirus vaccine in case- and control-patients respectively. The unmatched vaccine effectiveness against hospitalisation for administration of at least one dose of either rotavirus vaccines was 92% (95% confidence interval [CI]: 75%, 98%). The matched analyses by age only and both age and admission date showed 96% (95% CI: 72%, 100%) and 89% (95% CI: 51%, 97%) protection against rotavirus hospitalisation respectively. CONCLUSIONS: Rotavirus vaccine is highly effective in preventing hospitalisation from rotavirus disease in young Hong Kong children.