Severe microcephaly

Gene: YIPF5

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

Created: 10 Mar 2022, 1:37 p.m. | Last Modified: 10 Mar 2022, 1:37 p.m.

Panel Version: 2.292

Comment on list classification: New gene added and rated Green by Zornitza Stark. Sufficient evidence and appropriate phenotype (all affected individuals present progressive severe microcephaly, generalised tonic clonic seizures with onset at 1 - 7 months, diabetes diagnosed at 4 weeks - 15 months, and 5/6 also had severe DD) for inclusion on this panel: 6 patients from 5 families with different YIPF5 variants identified in PMID: 33164986. Functional analysis demonstrated that YIPF5 deficiency enhances ER stress and sensitises beta-cells to ER stress-induced apoptosis.

YIPF5 is also associated with a relevant phenotype in OMIM (MIM# 619278) but is not yet listed in G2P.

There is enough evidence to rate this gene as Green at the next GMS panel update.

Created: 19 May 2021, 2:04 p.m. | Last Modified: 19 May 2021, 2:04 p.m.

Panel Version: 2.170

Green List (high evidence)

Six individuals from 5 unrelated consanguineous families reported with bi-allelic variants in this gene and neonatal/early-onset diabetes, severe microcephaly, and epilepsy. Functional data supports gene-disease association.
Sources: Literature

Created: 9 Dec 2020, 7:29 a.m.

Mode of inheritance
BIALLELIC, autosomal or pseudoautosomal

Phenotypes
Neonatal diabetes; microcephaly; seizures

Publications

• 33164986