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Improving Student Outcomes with an Adaptable Molecular Cloning Course-Based Undergraduate Research Experience
Published on: November 15, 2024
Clinical Features, Molecular Genetics, and Long-Term Outcome in Congenital Chloride Diarrhea: A Nationwide Study in
Ken-Ichiro Konishi1, Tatsuki Mizuochi2, Tadahiro Yanagi2
1Department of Pediatrics and Child Health, Kurume University School of Medicine, Kurume, Japan; Department of Pediatric Surgery, Graduate School of Medicine, The University of Tokyo, Tokyo, Japan.
Insights
This study clarifies congenital chloride diarrhea (CCD) in Japanese children, identifying SLC26A3 mutations and highlighting early diagnosis and supplementation as key management strategies.
Area of Science:
- Pediatrics
- Genetics
- Gastroenterology
Background:
- Congenital chloride diarrhea (CCD) is a rare inherited disorder affecting intestinal ion transport.
- Accurate clinical and genetic characterization is crucial for timely diagnosis and management.
Purpose of the Study:
- To elucidate the clinical manifestations and genetic landscape of congenital chloride diarrhea in Japanese pediatric patients.
- To identify common mutations in the SLC26A3 gene associated with CCD in this population.
Main Methods:
- A retrospective survey was conducted across 616 pediatric centers in Japan from 2014 to 2018.
- Genetic analysis involved Sanger sequencing to detect mutations in the SLC26A3 gene.
- Clinical data and follow-up information were collected for patients meeting diagnostic criteria.
Main Results:
- Thirteen patients with confirmed SLC26A3 mutations and 14 meeting clinical criteria were identified.
- 93% of patients had homozygous or compound heterozygous SLC26A3 mutations, including 6 novel variants.
- The c.2063-1g>t mutation was the most frequent, potentially indicating a founder effect in East Asia.
- Most patients were diagnosed neonatally, with good neurodevelopment and manageable chronic kidney disease.
- Long-term electrolyte supplementation was required for a significant proportion of patients.
Conclusions:
- Genetic analysis of SLC26A3 is definitive for diagnosing congenital chloride diarrhea.
- Early fetal ultrasound diagnosis and prompt electrolyte supplementation are vital management components.
- The c.2063-1g>t mutation may represent a founder mutation in the East Asian population.
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.
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