1. Novel synonymous and missense variants in FGFR1 causing Hartsfield syndrome
- Author
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Marta Owczarek-Lipska, Aleksander Jamsheer, Fanny Dallèves, Erik Riesch, Lucjusz Jakubowski, Anna Sowińska-Seidler, John Neidhardt, Christopher B. Jackson, Carolina Courage, Johannes R. Lemke, and Małgorzata Piotrowicz
- Subjects
FGFR1, fibroblast growth factor receptor 1, gonadal mosaicism, Hartsfield syndrome,holoprosencephaly ,Isolated hypogonadotropic hypogonadism ,Male ,Ectrodactyly ,Cleft Lip ,DNA Mutational Analysis ,Mutation, Missense ,Germline mosaicism ,Trigonocephaly ,Fingers ,03 medical and health sciences ,Hypogonadotropic hypogonadism ,Intellectual Disability ,Holoprosencephaly ,Genetics ,medicine ,Missense mutation ,Humans ,Genetic Predisposition to Disease ,ddc:610 ,Receptor, Fibroblast Growth Factor, Type 1 ,Genetics (clinical) ,Exome sequencing ,Genetic Association Studies ,Silent Mutation ,030304 developmental biology ,0303 health sciences ,business.industry ,030305 genetics & heredity ,medicine.disease ,3. Good health ,Pedigree ,Cleft Palate ,Phenotype ,Pfeiffer syndrome ,Female ,business ,Hand Deformities, Congenital - 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).
- Published
- 2019