Novel heterozygous mutation in the extracellular domain of FGFR1 associated with Hartsfield syndrome

Masaki Takagi; Tatsuya Miyoshi; Yuka Nagashima; Nao Shibata; Hiroko Yagi; Ryuji Fukuzawa; Tomonobu Hasegawa

doi:10.1038/hgv.2016.34

Novel heterozygous mutation in the extracellular domain of FGFR1 associated with Hartsfield syndrome

Hum Genome Var. 2016 Oct 13:3:16034. doi: 10.1038/hgv.2016.34. eCollection 2016.

Authors

Masaki Takagi¹, Tatsuya Miyoshi², Yuka Nagashima³, Nao Shibata³, Hiroko Yagi³, Ryuji Fukuzawa⁴, Tomonobu Hasegawa⁵

Affiliations

¹ Department of Pediatrics, Keio University School of Medicine, Tokyo, Japan; Department of Pathology and Laboratory Medicine, Tokyo Metropolitan Children's Medical Center, Tokyo, Japan.
² Department of Endocrinology and Metabolism, Shikoku Medical Center for Children and Adults , Kagawa, Japan.
³ Department of Endocrinology and Metabolism, Tokyo Metropolitan Children's Medical Center , Tokyo, Japan.
⁴ Department of Pathology and Laboratory Medicine, Tokyo Metropolitan Children's Medical Center , Tokyo, Japan.
⁵ Department of Pediatrics, Keio University School of Medicine , Tokyo, Japan.

Abstract

Heterozygous kinase domain mutations or homozygous extracellular domain mutations in FGFR1 have been reported to cause Hartsfield syndrome (HS), which is characterized by the triad of holoprosencephaly, ectrodactyly and cleft lip/palate. To date, more than 200 mutations in FGFR1 have been described; however, only 10 HS-associated mutations have been reported thus far. We describe a case of typical HS with hypogonadotropic hypogonadism (HH) harboring a novel heterozygous mutation, p.His253Pro, in the extracellular domain of FGFR1. This is the first report of an HS-associated heterozygous mutation located in the extracellular domain of FGFR1, thus expanding our understanding of the phenotypic features and further developmental course associated with FGFR1 mutations.