Severe microcephalyGene: YIF1B
Comment on list classification: Although 5/6 individuals described in PMID:32006098 had microcephaly, 4 of these share the same founder variant and the severity of microcephaly is not specified. Therefore, rating Amber until further cases are reported (added to watchlist).
Created: 6 Oct 2020, 3:31 p.m. | Last Modified: 6 Oct 2020, 3:31 p.m.
Panel Version: 2.27
6 individuals (from 5 families) with biallelic YIF1B truncating variants reported. Presenting features: hypotonia, failure to thrive, microcephaly (5/6), severe global DD and ID as well as features suggestive of a motor disorder (dystonia/spasticity/dyskinesia). Seizures were reported in 2 unrelated individuals (2/6). MRI abnormalities were observed in some with thin CC being a feature in 3. Affected individuals were found to be homozygous for truncating variants (4/5 families being consanguineous). The following 3 variants were identified (NM_001039672.2) : c.186dupT or p.Ala64fs / c.360_361insACAT or p.Gly121fs / c.598G>T or p.Glu200*. Yif1B KO mice demonstrate a disorganized Golgi architecture in pyramidal hippocampal neurons (Alterio et al 2015 - PMID: 26077767). Functional/network analysis of genes co-regulated with YIF1B based on available RNAseq data, suggest enrichement in in genes important for nervous system development and function.
Sources: Expert list
Created: 4 Sep 2020, 10:46 a.m.
Mode of inheritance
BIALLELIC, autosomal or pseudoautosomal
Central hypotonia; Failure to thrive; Microcephaly; Global developmental delay; Intellectual disability; Seizures; Spasticity; Abnormality of movement
Variants in this GENE are reported as part of current diagnostic practice
Tag for-review was removed from gene: YIF1B. Tag watchlist tag was added to gene: YIF1B.
Tag for-review tag was added to gene: YIF1B.
Gene: yif1b has been classified as Amber List (Moderate Evidence).
gene: YIF1B was added gene: YIF1B was added to Severe microcephaly. Sources: Expert list Mode of inheritance for gene: YIF1B was set to BIALLELIC, autosomal or pseudoautosomal Publications for gene: YIF1B were set to 32006098; 26077767 Phenotypes for gene: YIF1B were set to Central hypotonia; Failure to thrive; Microcephaly; Global developmental delay; Intellectual disability; Seizures; Spasticity; Abnormality of movement Review for gene: YIF1B was set to GREEN gene: YIF1B was marked as current diagnostic