Novel synonymous and missense variants in FGFR1 causing Hartsfield syndrome. Issue 12 (11th September 2019)

• Record Type: Journal Article
• Authors: Courage, Carolina; Jackson, Christopher B.; Owczarek‐Lipska, Marta; Jamsheer, Aleksander; Sowińska‐Seidler, Anna; Piotrowicz, Małgorzata; Jakubowski, Lucjusz; Dallèves, Fanny; Riesch, Erik; Neidhardt, John; Lemke, Johannes R.
• Is Part Of: American journal of medical genetics. Volume 179:Issue 12(2019)
• Page Start: 2447
• Page End: 2453
• Publication Date: 2019-09-11
• Subjects: FGFR1 -- fibroblast growth factor receptor 1 -- gonadal mosaicism -- Hartsfield syndrome -- holoprosencephaly; Medical genetics -- Periodicals; 616.14205
• DOI: 10.1002/ajmg.a.61354
• Languages: English
• ISSNs: 1552-4825

Abstract

Abstract: Hartsfield syndrome is a rare clinical entity characterized by holoprosencephaly and ectrodactyly with the variable feature of cleft lip/palate. In addition to these symptoms patients with Hartsfield syndrome can show developmental delay of variable severity, isolated hypogonadotropic hypogonadism, central diabetes insipidus, vertebral anomalies, eye anomalies, and cardiac malformations. Pathogenic variants in FGFR1 have been described to cause phenotypically different FGFR1 ‐related disorders such as Hartsfield syndrome, hypogonadotropic hypogonadism with or without anosmia, Jackson–Weiss syndrome, osteoglophonic dysplasia, Pfeiffer syndrome, and trigonocephaly Type 1. Here, we report three patients with Hartsfield syndrome from two unrelated families. Exome sequencing revealed two siblings harboring a novel de novo heterozygous synonymous variant c.1029G>A, p.Ala343Ala causing a cryptic splice donor site in exon 8 of FGFR1 likely due to gonadal mosaicism in one parent. The third case was a sporadic patient with a novel de novo heterozygous missense variant c.1868A>G, p.(Asp623Gly).