RESUMO
OBJECTIVE: To clarify clinical and genetic features of Japanese children with congenital chloride diarrhea (CCD). STUDY DESIGN: This was a multi-institutional, retrospective survey of 616 pediatric centers in Japan with identified patients with CCD between 2014 and 2018. Mutations involving SLC26A3 were detected by Sanger sequencing. RESULTS: Thirteen patients met all entry criteria including mutations in SLC26A3, and 14 patients satisfied clinical diagnostic criteria. Homozygous or compound heterozygous mutations in SLC26A3, including 6 novel mutations, were identified in 13 of these 14 patients (93%). The most common (detected in 7 of 13) was c.2063-1g>t. Median age at diagnosis was 1 day. Nine of the patients meeting all criteria were diagnosed as neonates (69%). Median follow-up duration was 10 years. When studied, 8 patients had <5 stools daily (62%), and all had fewer than in infancy. Only 1 patient had nephrocalcinosis, and 3 (23%) had mild chronic kidney disease. Neurodevelopment was generally good; only 1 patient required special education. Five patients (38%) received long-term sodium, potassium, and chloride supplementation. CONCLUSIONS: Early fetal ultrasound diagnosis and prompt long-term sodium, potassium, and chloride supplementation were common management features. Genetic analysis of SLC26A3 provided definitive diagnosis of CCD. In contrast with previously reported localities, c.2063-1g>t might be a founder mutation in East Asia.
Assuntos
Antiportadores de Cloreto-Bicarbonato/genética , DNA/genética , Diarreia/congênito , Previsões , Erros Inatos do Metabolismo/genética , Mutação , Vigilância da População , Transportadores de Sulfato/genética , Antiportadores de Cloreto-Bicarbonato/metabolismo , Análise Mutacional de DNA , Diarreia/epidemiologia , Diarreia/genética , Diarreia/metabolismo , Feminino , Seguimentos , Testes Genéticos , Humanos , Incidência , Recém-Nascido , Japão/epidemiologia , Masculino , Erros Inatos do Metabolismo/epidemiologia , Erros Inatos do Metabolismo/metabolismo , Estudos Retrospectivos , Transportadores de Sulfato/metabolismo , Taxa de Sobrevida/tendências , Fatores de TranscriçãoRESUMO
OBJECTIVE: To identify cytokine genes uniquely expressed in peripheral blood mononuclear cells (PBMNCs) in the acute phase of Kawasaki disease (KD) with coronary artery lesions (CALs). STUDY DESIGN: We screened the mRNA expression levels of PBMNCs from 4 pairs of KD patients with and without CAL using DNA microarray. The result was confirmed by real-time polymerase chain reaction (RT-PCR). The genetic association study was performed to analyze the significance of single nucleotide polymorphisms in the identified gene for the development of CAL in KD patients (184 controls, 144 KD patients with CAL, 64 KD patients without CAL). RESULTS: The microarray analysis showed that tissue inhibitor of metalloproteinases 2 (TIMP2) was expressed at higher levels in PBMNCs of KD patients with CAL than in KD patients without CAL. Quantitative RT-PCR confirmed that the expression levels were significantly higher in the KD patients with CAL than in those without CAL (P < .05). Among KD patients, TIMP2 promoter polymorphisms were significantly associated with a risk of CAL (P < .01). There was a significant difference in the transcriptional activities between the haplotypes of the TIMP2 promoter polymorphisms by reporter assay using U-937. CONCLUSIONS: TIMP2 overexpression and the promoter polymorphisms might play a role in the development of CALs.