Intestinal failure or congenital diarrhoea

Gene: DGAT1

This gene has been confirmed for this panel by the NHS Genomic Medicine Service and should be rated green.

Created: 8 Mar 2022, 11:44 a.m. | Last Modified: 8 Mar 2022, 11:44 a.m.

Panel Version: 1.48

Green List (high evidence)

Haas et al 2012 identified 2 siblings (Ashkenazi Jewish descent) with congenital diarrheal disorder. They used exome sequencing to identify homozygous loss-of-function DGAT1 mutations.
Stephen et al 2016 used homozygosity mapping and exome sequencing in 3 affected children from 2 families with severe diarrhea, hypoalbuminemia and protein-losing enteropathy. They found homozygous DGAT1 mutations in both families.
Gluchowski et al 2017 used exome sequencing on 2 identical Asian male twins with watery diarrhea shortly after birth, protein-losing enteropathy and failure to thrive. They found a homozygous recessive mutation in DGAT1, c.314T>C, p.L105P. Functional studies showed the enzyme produced from the mutant allele is less abundant, resulting in partial loss of TG synthesis activity and decreased formation of lipid droplets in patient-derived primary dermal fibroblasts. Thus, in contrast with complete loss-of-function alleles of DGAT1, the p.L105P missense allele partially reduces TG synthesis activity and causes a less severe clinical phenotype
Ratchford 2018 identified compound heterozygous mutations in Caucasian girl with severe congenital diarrhea.

Created: 22 Jan 2019, 1:39 p.m.

Mode of inheritance
BIALLELIC, autosomal or pseudoautosomal

Phenotypes
Congenital diarrheal disorder

Publications

• PMID: 23114594
• 26883093
• 28937539
• 28373485

Green List (high evidence)

Comment when marking as ready: As discussed in the GMS Gastrohepatology Specialist Test Group webex call 14th Jan 2019: The Specialist Test Group agreed that there is enough evidence to rate this gene green.

Created: 24 Jan 2019, 4:34 p.m.

Initial gene list and info collated by Miranda Durkie Sheffield Diagnostic Genetics Service December 2018 on behalf of the GMS Gastrohepatology specialist test group. Gene Symbol submitted: DGAT1; Suggested intial gene rating: Green; Evidence for inclusion: none given; Evidence for exclusion: none given; Technical notes (e.g. non-coding/CNV mutations requiring coverage?): none given

Created: 8 Jan 2019, 10:52 a.m.