CNNM4 was first reported in relation to autosomal recessive Jalili syndrome which causes cone rod dystrophy and amelogenesis imperfecta (AI) in 2009 (Parry et al., 19200525). At least four missense variants, three nonsense variants, and one frameshift variant have been reported in humans. Variants in this gene have been reported in at least 10 probands in 2 publications (19200525, 19200527). Variants in this gene segregated with disease in 33 additional family members. Evidence supporting this gene-disease relationship includes case-level data, segregation data, and experimental data. More evidence is available in the literature, but the maximum score for genetic evidence and/or experimental evidence (12 pts.) has been reached. This gene-disease association is supported by several lines of experimental evidence including the expression of CNNM4 in retina and incisors in mice (19200525, 19200527), enamel defects similar to AI in a mouse model (24339795), along with rescue studies in zebrafish (19200527). In summary, CNNM4 is definitively associated with autosomal recessive Jalili syndrome. This has been repeatedly demonstrated in both the research and clinical diagnostic settings, and has been upheld over time.
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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