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case-control·pediatrics, nutrition, micronutrients, vitamins, clinical trial·PMC10522106

Maternal Vitamin A Status as a Risk Factor of Hirschsprung Disease in the Child

Clinical and Translational Gastroenterology · 7 authors, 4 centres

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TL;DR

The findings suggest lower maternal vitamin A status may be a risk factor for HSCR and could interact with genetic variants to influence disease penetrance.

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The findings suggest lower maternal vitamin A status may be a risk factor for HSCR and could interact with genetic variants to influence disease penetrance.

STUDY TYPE

case-control

SPECIALTY

pediatrics

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AI pipeline

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100% · A

ORIGINAL PAPER

PMC10522106

Maternal Vitamin A Status as a Risk Factor of Hirschsprung Disease in the Child

Clinical and Translational Gastroenterology

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ABSTRACT

Abstract INTRODUCTION: The gene-environment interaction of the REarranged during Transfection ( RET ) gene with vitamin A in the etiopathogenesis of Hirschsprung disease (HSCR) has been suggested in rodents. The aim of this study was to evaluate vitamin A status in mothers of children with HSCR and to assess its association with pathogenic variants of the RET gene in affected children. METHODS: This was a case-control study of stable isotope–based vitamin A measurement stores of mothers of children diagnosed with HSCR (within 8 months from birth, n = 7) and age-matched mothers of normal children (n = 6). Next-generation sequencing of RET exons, along with their upstream promoter region, was performed in the 7 HSCR proband-parent triads to evaluate pathogenic variants. RESULTS: Maternal vitamin A stores in the HSCR group was almost 50% that of those in controls, tending toward significance (0.50 ± 0.17 vs 0.89 ± 0.51 μmol/g respectively, P = 0.079). Two novel pathogenic de novo mutations were identified in 2 cases, and a rare single-nucleotide deletion was detected in the 3.5-kb RET upstream region, in a heterozygous state, in all 7 proband-parent triads. Low-penetrance RET haplotypes associated with HSCR were detected in 5 cases. DISCUSSION: Mothers with children with HSCR had lower vitamin A liver stores than mothers with normal children, and the children who were affected had HSCR despite having no established pathogenic RET variants. Lower maternal vitamin A status may increase the penetrance of genetic mutations in RET , and vitamin-A mediated gene-environment interactions may underpin some of the etiology of HSCR. KEYWORDS: Hirschsprung disease, RET proto-oncogene, vitamin A, gene-environment interaction, stable isotope

CITATION EXPORT

Shalini G Hegde, Sarita Devi, Ambily Sivadas et al.. Maternal Vitamin A Status as a Risk Factor of Hirschsprung Disease in the Child. Clinical and Translational Gastroenterology. (2023). https://doi.org/10.14309/ctg.0000000000000619

AUTHORS

7 · 4 CENTRES

Shalini G Hegde, Sarita Devi, Ambily Sivadas, Attibele Mahadevaiah Shubha, Annamma Thomas, Arpita Mukhopadhyay, Anura V Kurpad

1Department of Paediatric Surgery, St. John's Medical College Hospital, Bangalore, India;
2Division of Nutrition, St. John's Research Institute, Bangalore, India;
3Department of Obstetrics and Gynaecology, St. John's Medical College Hospital, Bangalore, India;
4Department of Physiology, St. John's Medical College Hospital, Bangalore, India.