The MAB21L1 gene, located on chromosome 13 at 13q13.3, encodes the mab-21 like 1 protein which is a putative nucleotidyltransferase required for several aspects of embryonic development including normal development of the eye. MAB21L1 was first reported in relation to autosomal recessive cerebellar, ocular, craniofacial, and genital syndrome (COFG) in 2017 (Bruel et al., PMID: 27103078). COFG is characterized by cerebellar hypoplasia with ataxia, ocular anomalies, facial dysmorphism, scrotal agenesis, absent or underdeveloped nipples and underdeveloped labioscrotal folds, accompanied by moderate to severe developmental delay and intellectual disability. The mechanism of disease is reported to be loss of function. At least six unique variants (missense, nonsense, frameshift) that have been reported in a homozygous statein 11 individuals from six consanguineous families in two publications (PMIDs: 27103078, 30487245) are included in this curation. Variants in this gene segregated in seven additional family members in two families (PMID: 30487245, 27075597). This gene-disease relationship is also supported by evidence of persistent and restricted expression of Mab21l1 to the cerebellum and eye in mouse, and a mouse model which displayed eye and preputial gland anomalies (PMIDs: 10349626, 25434003). In summary, there is strong evidence to support the relationship between MAB21L and autosomal recessive cerebellar, ocular, craniofacial, and genital syndrome. Three years must elapse from the first proposal of the assertion 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 classification was approved by the ClinGen Syndromic GCEP on the meeting date April 19th, 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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