Severe microcephaly

Gene: CCDC88A

Green List (high evidence)

The rating of this gene has been updated to green following NHS Genomic Medicine Service approval.

Created: 24 Feb 2025, 5:58 p.m. | Last Modified: 24 Feb 2025, 5:58 p.m.

Panel Version: 7.12

Mode of inheritance
BIALLELIC, autosomal or pseudoautosomal

Comment on list classification: There are now at least 7 individuals from 4 unrelated families with biallelic variants in the CCDC88A gene (PMID: 26917597; 30392057; 37798908; 39334473), described to a PEHO-like syndrome with universal features including ID, epilepsy, microcephaly and optic nerve/cerebellar atrophy.

Sufficient unrelated cases with the same phenotype to promote this gene to green at the next GMS panel update.

Created: 6 Nov 2024, 4:24 p.m. | Last Modified: 6 Nov 2024, 4:24 p.m.

Panel Version: 7.2

I don't know

PMID:26917597 - 3 children, single family encephalopathy, seizures, progressive. microcephaly. Truncating variants. PMID:30392057 - consanguineous family, homozygous nonsense, phenotype of DD, epilepsy, optic atrophy, pedal oedema. Two families, progressive microcephaly outlined in one . Provisionally rated Amber.

Created: 10 Oct 2019, 10:30 a.m. | Last Modified: 10 Oct 2019, 10:30 a.m.

Panel Version: 1.74

Mode of inheritance
BIALLELIC, autosomal or pseudoautosomal

Phenotypes
?PEHO syndrome-like, 617507

Publications

• 26917597
• 30392057

I don't know

Comment on list classification: Gene rated Amber- this rating was suggested in an email to the test group on 6th November after review by Genomics England clinical team review, and indicating if there were no further comments on the rating the gene would rated as per provisional suggestion as per recommended on the current evidence in the literature

Created: 27 Nov 2019, 3:11 p.m. | Last Modified: 27 Nov 2019, 3:11 p.m.

Panel Version: 1.75

As discussed with the GMS Neurology Specialist Test Group webex call 11th July 2019: New gene and Green rating recommended to be added to panel by Steve Abbs (Consultant Clinical Scientist, East Anglia Medical Genetics Service) on behalf of Geoff Woods (Cambridge Institute for Medical research). PanelApp team added gene /phenotype and MOI from OMIM to panel and requested evidence for the proposed rating before gene can be upgraded to Green.
Sources: Expert list

Created: 29 Jul 2019, 3:09 p.m.

Mode of inheritance
BIALLELIC, autosomal or pseudoautosomal

Phenotypes
PEHO syndrome-like, 617507