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: 31 Jan 2019, 10:33 a.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: BAAT; 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: 7 Jan 2019, 4:42 p.m.
Comment on list classification: Changed Amber to Green from external expert review and further publications to support gene-disease association
Created: 25 Jul 2018, 10:36 a.m.
Comment on mode of inheritance: Setchell KD et al. (2013) PMID: 23415802. In each family in which a BAAT mutation was detected, the affected children were found to be homozygous for the familial mutation, and other unaffected family members were heterozygous, or did not carry the mutation. These results indicate that this amidation defect behaves as an autosomal recessive trait.
Created: 25 Jul 2018, 10:25 a.m.
Comment on publications: Setchell KD et al. (2013) PMID: 23415802 investigated the clinical, biochemical, molecular, and morphologic features of a genetic defect in bile acid conjugation in 10 pediatric patients with fat-soluble vitamin deficiency, some with growth failure or transient neonatal cholestatic hepatitis. They dentified the genetic defect that causes this disorder using mass spectrometry analysis of urine, bile, and serum samples and sequence analysis of the genes encoding bile acid-CoA: amino acid N-acyltransferase (BAAT) and bile acid-CoA ligase (SLC27A5). Molecular analysis of BAAT confirmed 3 different homozygous missense mutations, the patients were from Saudi Arabia/Asian; USA/Hispanic; USA/Amish . Of interest is that BAAT mutation in Patient #8, who is Amish, is different from the BAAT mutation previously reported in individuals with Lancaster County Old Order Amish ancestry, consistent with the finding of genetic heterogeneity for some other rare genetic disorders amongst the Amish. This publication reports additional cases that are not of Amish origin.
Created: 25 Jul 2018, 10:08 a.m.
Comment on mode of inheritance: Carlton et al. (2003) postulated oligogenic inheritance of familial hypercholanemia, oligogenic inheritance represents an intermediate between monogenic inheritance in which a trait is determined by a single causative gene, and polygenic inheritance, in which a trait is influenced by many genes and often environmental factors. However external expert reviewer (the gene is reported as part of current diagnostic practice) and Orphanet denote Autosomal recessive (Bialleleic inheritance).
Created: 25 Jul 2018, 9:50 a.m.
Comment on publications: from OMIM added publication Carlton et al. (2003) PMID: 12704386 studied this disorder in 17 individuals in 12 families of Lancaster County Old Order Amish descent. In 6 families, affected individuals were homozygous for a missense mutation in the gene encoding tight junction protein-2 (TJP2; 607709.0001). In 2 families, affected individuals were homozygous for an M76V mutation in the BAAT gene (602938.0001). In 2 families, the affected individuals were homozygous for the TJP2 missense mutation and heterozygous for the BAAT mutation, and in 1 family affected individuals were homozygous for the BAAT mutation and heterozygous for the TJP2 mutation. Carlton et al. (2003) postulated oligogenic inheritance of familial hypercholanemia.
Created: 25 Jul 2018, 9:48 a.m.
from Orphanet; Familial hypercholanemia is a very rare genetic disorder characterized clinically by elevated serum bile acid concentrations, itching, and fat malabsorption reported in patients of Old Order Amish descent.
Created: 25 Jul 2018, 9:44 a.m.
Comment on phenotypes: added phenotypes from OMIM and external clinical review
Created: 25 Jul 2018, 9:39 a.m.
Mode of inheritance
BIALLELIC, autosomal or pseudoautosomal
cholestasis; fat soluble vitamin deficiency
Variants in this GENE are reported as part of current diagnostic practice
Gene: baat has been classified as Green List (High Evidence).
Source Other was added to BAAT. Mode of inheritance for gene BAAT was changed from to BIALLELIC, autosomal or pseudoautosomal Added phenotypes Hypercholanemia, Familial; Hypercholanemia, familial, 607748; fat soluble vitamin deficiency; Neonatal and Adult Cholestasis; cholestasis for gene: BAAT Publications for gene BAAT were changed from to 23415802; 12704386
Source Expert Review Green was added to BAAT. Rating Changed from Red List (low evidence) to Green List (high evidence)
gene: BAAT was added gene: BAAT was added to Cholestasis. Sources: NHS GMS Mode of inheritance for gene: BAAT was set to