MSX2 was first associated with autosomal dominant craniosynostosis by Warman et al. in 1993 (PMID: 8357019). The large family originally described was studied in Boston thus their phenotype has since been referred to as "craniosynostosis, Boston type" or "craniosynostosis, Warman type" (PMID: 23949913, 23918290). At least 3 unique missense variants have been identified in patients with craniosynostosis (PMIDs: 8357019, 23918290, 23949913, 27884935, 28808027). Notably, all variants are at the Pro148 codon in exon 2. Evidence supporting this gene-disease relationship includes case-level, segregation, and experimental evidence. Two mouse models have been generated, thus reaching the maximum score of 4 pts has been reached for animal models (PMIDs: 9917362, 7597092). In summary, MSX2 is definitively associated with autosomal dominant craniosynostosis. 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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