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Eur J Med Genet. 2019 Oct 9:103784. doi: 10.1016/j.ejmg.2019.103784. [Epub ahead of print]

A de novo frameshift FGFR1 mutation extending the protein in an individual with multiple epiphyseal dysplasia and hypogonadotropic hypogonadism without anosmia.

Author information

1
Division of Medical Genetics, Department of Pediatrics, CHU Sainte-Justine Hospital, University of Montreal, Montreal, Canada.
2
Division of Endocrinology, Department of Pediatrics, CHU Sainte-Justine Hospital, University of Montreal, Montreal, Canada.
3
Division of Orthopaedic Surgery, Department of Pediatrics, CHU Sainte-Justine Hospital, University of Montreal, Montreal, Canada.
4
Department of Pediatrics, Shriners Hospital for Children, McGill University, Montreal, Canada.
5
Division of Medical Genetics, Department of Pediatrics, CHU Sainte-Justine Hospital, University of Montreal, Montreal, Canada. Electronic address: p.campeau@umontreal.ca.

Abstract

Multiple epiphyseal dysplasia (MED) is a genetically and clinically heterogeneous disease with both dominant and recessive inheritance. Eight different genes are known to cause the disease but in 15% of cases of MED, no mutation is found. Fibroblast growth factor receptor 1 (FGFR1) is a crucial regulator of bone formation and when mutated, can cause diseases with skeletal manifestations; nevertheless, MED has not been described in individuals with FGFR1 mutations. In this report, we describe a proband with MED and congenital normosmic hypogonadotropic hypogonadism (HH). DNA analysis showed a de novo frameshift variant in FGFR1 likely explaining the HH (p.Arg852Thrfs*165). No other mutation was found after a large gene sequencing panel, exome sequencing and an array CGH, except for a variant of unknown significance in FBN1 (rs755375255), but there were no features of a disease associated with FBN1 mutations and this variant is found a few times in population databases. We thus discuss the possibility that MED might be a new skeletal feature associated with FGFR1 mutations.

KEYWORDS:

FGFR1; Fibroblast growth factor receptor 1; Hypogonadotropic hypogonadism; MED; Multiple epiphyseal dysplasia

PMID:
31605817
DOI:
10.1016/j.ejmg.2019.103784

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