A novel variant of FGFR3 causes proportionate short stature

European Journal of Endocrinology
Sarina G KantM Losekoot

Abstract

Mutations of the fibroblast growth factor receptor 3 (FGFR3) cause various forms of short stature, of which the least severe phenotype is hypochondroplasia, mainly characterized by disproportionate short stature. Testing for an FGFR3 mutation is currently not part of routine diagnostic testing in children with short stature without disproportion. A three-generation family A with dominantly transmitted proportionate short stature was studied by whole-exome sequencing to identify the causal gene mutation. Functional studies and protein modeling studies were performed to confirm the pathogenicity of the mutation found in FGFR3. We performed Sanger sequencing in a second family B with dominant proportionate short stature and identified a rare variant in FGFR3. Exome sequencing and/or Sanger sequencing was performed, followed by functional studies using transfection of the mutant FGFR3 into cultured cells; homology modeling was used to construct a three-dimensional model of the two FGFR3 variants. A novel p.M528I mutation in FGFR3 was detected in family A, which segregates with short stature and proved to be activating in vitro. In family B, a rare variant (p.F384L) was found in FGFR3, which did not segregate with short stature and ...Continue Reading

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Citations

Nov 19, 2015·European Journal of Endocrinology·Jan M WitSarina G Kant
Oct 7, 2015·Nature Reviews. Endocrinology·Jeffrey BaronOla Nilsson
Dec 18, 2016·Developmental Dynamics : an Official Publication of the American Association of Anatomists·David M Ornitz, Laurence Legeai-Mallet
May 13, 2017·Annales d'endocrinologie·Agnès LinglartCatherine Adamsbaum
Mar 24, 2017·Hormone Research in Pædiatrics·Anenisia C AndradeOla Nilsson
Jun 30, 2016·Endocrine Reviews·Antonio MarchiniGudrun A Rappold
Oct 13, 2017·Annals of Pediatric Endocrinology & Metabolism·Min Jae Kang
Aug 24, 2019·Current Osteoporosis Reports·Pushpanathan Muthuirulan, Terence D Capellini
Feb 14, 2019·Scientific Reports·Isabel S JerchelMonique L den Boer
Jun 7, 2020·Endocrine·Maria Felicia FaienzaGabriele D'Amato
Jan 5, 2019·Orphanet Journal of Rare Diseases·Richard M Pauli
Mar 14, 2019·Archives of Endocrinology and Metabolism·Gabriela A VasquesAlexander A L Jorge
May 7, 2021·Science Translational Medicine·Takeshi KimuraPavel Krejci
Jul 30, 2015·Genes & Development·David M Ornitz, Pierre J Marie

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