Novel synonymous and missense variants in FGFR1 causing Hartsfield syndrome.

Authors

Courage C^1,2, Jackson CB³, Owczarek-Lipska M⁴, Jamsheer A^5,6, Sowińska-Seidler A⁵, Piotrowicz M⁷, Jakubowski L⁷, Dallèves F², Riesch E⁸, Neidhardt J⁴, Lemke JR⁹.

Folkhälsan Research Center, Helsinki, Finland.
Division of Human Genetics, Department of Pediatrics, Inselspital, University of Bern, Bern, Switzerland.
Stem Cells and Metabolism Research Program, Faculty of Medicine, University of Helsinki, Helsinki, Finland.
Human Genetics, Faculty of Medicine and Health Sciences, University of Oldenburg, Oldenburg, Germany.
Department of Medical Genetics, Poznan University of Medical Sciences, Poznan, Poland.
Centers for Medical Genetics GENESIS, Poznan, Poland.
Department of Genetics, Polish Mother’s Memorial Hospital Research Institute, Poland
CeGaT GmbH-Center for Genomics and Transcriptomics, Tübingen, Germany.
Institute of Human Genetics, University of Leipzig Medical Center, Leipzig, Germany.

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).

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Novel synonymous and missense variants in FGFR1 causing Hartsfield syndrome.

Courage C^1,2, Jackson CB³, Owczarek-Lipska M⁴, Jamsheer A^5,6, Sowińska-Seidler A⁵, Piotrowicz M⁷, Jakubowski L⁷, Dallèves F², Riesch E⁸, Neidhardt J⁴, Lemke JR⁹.

Abstract

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Novel synonymous and missense variants in FGFR1 causing Hartsfield syndrome.

Courage C1,2, Jackson CB3, Owczarek-Lipska M4, Jamsheer A5,6, Sowińska-Seidler A5, Piotrowicz M7, Jakubowski L7, Dallèves F2, Riesch E8, Neidhardt J4, Lemke JR9.

Abstract

References

Genetic Diagnostics

Research & Pharma Solutions

Company

Courage C^1,2, Jackson CB³, Owczarek-Lipska M⁴, Jamsheer A^5,6, Sowińska-Seidler A⁵, Piotrowicz M⁷, Jakubowski L⁷, Dallèves F², Riesch E⁸, Neidhardt J⁴, Lemke JR⁹.