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Novel synonymous and missense variants in FGFR1 causing Hartsfield syndrome.
Journal article

Novel synonymous and missense variants in FGFR1 causing Hartsfield syndrome.

  • Courage C Folkhälsan Research Center, Helsinki, Finland.
  • Jackson CB Stem Cells and Metabolism Research Program, Faculty of Medicine, University of Helsinki, Helsinki, Finland.
  • Owczarek-Lipska M Human Genetics, Faculty of Medicine and Health Sciences, University of Oldenburg, Oldenburg, Germany.
  • Jamsheer A Department of Medical Genetics, Poznan University of Medical Sciences, Poznan, Poland.
  • Sowińska-Seidler A Department of Medical Genetics, Poznan University of Medical Sciences, Poznan, Poland.
  • Piotrowicz M Department of Genetics, Polish Mother's Memorial Hospital Research Institute, Poland.
  • Jakubowski L Department of Genetics, Polish Mother's Memorial Hospital Research Institute, Poland.
  • Dallèves F Division of Human Genetics, Department of Pediatrics, Inselspital, University of Bern, Bern, Switzerland.
  • Riesch E CeGaT GmbH-Center for Genomics and Transcriptomics, Tübingen, Germany.
  • Neidhardt J Human Genetics, Faculty of Medicine and Health Sciences, University of Oldenburg, Oldenburg, Germany.
  • Lemke JR Institute of Human Genetics, University of Leipzig Medical Center, Leipzig, Germany.
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  • 2019-09-13
Published in:
  • American journal of medical genetics. Part A. - 2019
FGFR1
Hartsfield syndrome
fibroblast growth factor receptor 1
gonadal mosaicism
holoprosencephaly
Cleft Lip
Cleft Palate
DNA Mutational Analysis
Female
Fingers
Genetic Association Studies
Genetic Predisposition to Disease
Hand Deformities, Congenital
Holoprosencephaly
Humans
Intellectual Disability
Male
Mutation, Missense
Pedigree
Phenotype
Receptor, Fibroblast Growth Factor, Type 1
Silent Mutation
English 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).
Language
  • English
Open access status
closed
Identifiers
Persistent URL
https://sonar.ch/global/documents/153908
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