ALX3 has been repeatedly described in association with autosomal recessive Frontonasal dysplasia 1 also known as Frontorhiny. Frontonasal dysplasia 1 is characterized by having a distinctive facial appearance with hypertelorism, broad nasal bridge, short nasal ridge, splayed nasal bones with bifid nasal tip, broad columella that attaches to the lip above the alae, widely separated slit-like nares, long philtrum with prominent bilateral swellings, and midline notch in the upper lip and alveolus. At least 1 missense, 2 nonsense, 1 splice acceptor, 1 deletion mutations have been reported in at least 5 probands from 4 publications (PMIDs: 19409524, 22106187, 29215096, 34098755) This gene disease association is also supported by experimental evidence including expression data and an animal model (PMID:20534379) . In summary ALX3 is definitively associated with autosomal recessive Frontonasal dysplasia 1. 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 Craniofacial Malformations Gene Curation Expert Panel on 10/13/2022. (SOP Version 9)
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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