Cholestasis

Gene: CYP27A1

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: 31 Jan 2019, 10:36 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: CYP27A1; 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 phenotypes: added OMIM MIMid

Created: 25 Jul 2018, 2:27 p.m.

Comment on list classification: >3 cases reported in PMID: 28937538 for neonatal cholestasis, and a green review.

Created: 25 Jul 2018, 10:30 a.m.

Comment on publications: PMID: 28937538 - 8 neonatal patients described with severe cholestasis with homozygous/compound heterozygous variants in this gene. For two patients parental origin of the variants was not confirmed. No patient harbored a putatively pathogenic mutation in genes other than CYP27A1 that have been implicated in cholestatic liver disease. Conclusions from the publication were "CTX manifest as neonatal cholestasis has a bile acid profile different from CTX manifest in later life, and thus may be overlooked". Other publications are multiple cases/families providing evidence for the role of this gene in CTX (Cerebrotendinous xanthomatosis).

Created: 25 Jul 2018, 10:22 a.m.

Comment on list classification: Enzyme involved in the first step of the bile synthesis pathway.

Created: 25 Jul 2018, 10:03 a.m.

Green List (high evidence)

Mode of inheritance
BIALLELIC, autosomal or pseudoautosomal

Phenotypes
severe neonatal cholestasis; cerebrotendinous xanthomatosis

Variants in this GENE are reported as part of current diagnostic practice