The YIF1B gene, located on chromosome 19 at 19q13.2, encodes a trafficking protein that belongs to the FinGER protein family and is involved in endoplasmic reticulum-to-Golgi trafficking. YIF1B was first reported in relation to autosomal recessive Kaya-Barakat-Masson syndrome (KABAMAS) in 2020 (Diaz et al. 2020, PMID: 33103737; AlMuhaizea et al. 2020, PMID: 32006098). KABAMAS is a severe neurodevelopmental disorder characterized by profoundly impaired global development with variable motor abnormalities, poor coordination resulting in the inability to sit or walk, impaired intellectual development with absent speech, poor eye contact, and feeding difficulties resulting in poor overall growth. More variable features include early-onset seizures, ocular anomalies, foot deformities, and nonspecific brain imaging findings. Dysmorphic features are generally not present. The disease generally presents at birth and may be lethal in infancy or childhood. The mechanism of disease is reported to be loss of function. At least ten unique variants (2 missense, 2 nonsense, 3 frameshift, 3 splice-site) that have been reported in 13 probands from four publications (PMIDs: 32006098, 33103737, 36435927, 36948290) are included in this curation. Most of the variants identified were homozygous occurrences in consanguineous families. More evidence is available in the literature (PMID: 34373908), but the maximum score allowed for genetic evidence has been reached (12 pts). This gene-disease relationship is also supported by expression data, functional alteration studies, and a Yif1b knockout mouse model (PMIDs: 18685031, 26077767, 32006098, 33103737). In summary, there is definitive evidence to support the relationship between YIF1B and autosomal recessive Kaya-Barakat-Masson syndrome. This has been repeatedly demonstrated in both the research and clinical diagnostic settings, and has been upheld over time. This classification was approved by the ClinGen Syndromic GCEP on the meeting date August 16th, 2024 (SOP Version 10).
The GenCC data are available free of restriction under a CC0 1.0 Universal (CC0 1.0) Public Domain Dedication. The GenCC requests that you give attribution to GenCC and the contributing sources whenever possible and appropriate. The accepted Flagship manuscript is now available from Genetics in Medicine (https://www.gimjournal.org/article/S1098-3600(22)00746-8/fulltext).
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