A de novo frameshift FGFR1 mutation extending the protein in an individual with multiple epiphyseal dysplasia and hypogonadotropic hypogonadism without anosmia |
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Affiliation: | Hospital de Clínicas de Porto Alegre, Universidade Federal do Rio Grande do Sul, Porto Alegre, Brazil |
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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. |
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Keywords: | Fibroblast growth factor receptor 1 Multiple epiphyseal dysplasia MED Hypogonadotropic hypogonadism |
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