MPZL2 was first associated with autosomal recessive nonsyndromic hearing loss as early as 2018 (Wesdorp et al., PMID: 29961571; Bademci et al., PMID: 29982980). At least three unique variants (nonsense and frameshift) have been reported in humans. Evidence supporting this gene-disease relationship includes case-level data, segregation data, and experimental data. Variants in this gene have been reported in at least 15 probands in 4 publications (PMID: 29961571, 29982980, 32203226, 33234333). Variants in this gene segregated with disease in at least 11 additional family members. More evidence is available in the literature, but the maximum score for genetic evidence has been reached. The mechanism of disease is suspected to be homozygous or compound heterozygous loss of function. This gene-disease association is supported by a mouse model and expression studies (PMID: 29961571, 29982980). In summary, there is strong evidence to support the relationship between MPZL2 and autosomal recessive nonsyndromic hearing loss. Three years must elapse from the first proposal of the association to reach a definitive classification without any valid contradictory evidence. We will re-evaluate this gene-disease relationship at that time to determine if an upgraded classification of definitive is warranted. This curation was approved by the Hearing Loss Gene Curation Expert Panel on 3/26/21 (SOP Version 8).
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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