The Use of Variant Maps to Explore Domain-Specific Mutations of FGFR1:

Here we describe the genotype-phenotype correlations of diseases caused by variants in Fibroblast Growth Factor Receptor 1(FGFR1) and report a novel, de novo variant in FGFR1 in an individual with multiple congenital anomalies. The probandpresented with bilateral cleft lip and palate, malformed auricles, and bilateral ectrodactylyof his hands and feet at birth. He was later diagnosed with diabetes insipidus, spastic quadriplegia, developmental delay, agenesisof the corpus callosum, and enlargement of the third cerebral ventricle. We noted the substantial phenotypic overlap with individuals with Hartsfield syndrome, the rare combination of holoprosencephalyand ectrodactyly. Sequencing of FGFR1 identified a previously unreported de novo variant in exon 11 (p.Gly487Cys), which we modeled to determine its predicted effect on the protein structure. Although it was not predicted to significantly alter protein foldingstability, it is possible this variant leads to the formation of nonnative intra- or inter...