| KANT, Sarina G., Iveta ČERVENKOVÁ, Lukáš BÁLEK, Lukáš TRANTÍREK, Gijs W. E. SANTEN, Martine C. de VRIES, Hermine A. van DUYVENVOORDE, Michiel J. R. van der WIELEN, Annemieke J. M. H. VERKERK, André G. UITTERLINDEN, Sabine E. HANNEMA, Jan M. WIT, Wilma OOSTDIJK, Pavel KREJČÍ a Monique LOSEKOOT. A novel variant of FGFR3 causes proportionate short stature. European Journal od Endocrinology. Bristol: Bioscientifica LTD, 2015, roč. 172, č. 6, s. 763-770. ISSN 0804-4643. doi:10.1530/EJE-14-0945. |
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@article{1306875,
author = {Kant, Sarina G. and Červenková, Iveta and Bálek, Lukáš and Trantírek, Lukáš and Santen, Gijs W. E. and Vries, Martine C. de and Duyvenvoorde, Hermine A. van and Wielen, Michiel J. R. van der and Verkerk, Annemieke J. M. H. and Uitterlinden, André G. and Hannema, Sabine E. and Wit, Jan M. and Oostdijk, Wilma and Krejčí, Pavel and Losekoot, Monique},
article_location = {Bristol},
article_number = {6},
doi = {http://dx.doi.org/10.1530/EJE-14-0945},
keywords = {FACTOR RECEPTOR-3 GENE; ASN540SER MUTATION; DUTCH CHILDREN; HYPOCHONDROPLASIA; ACTIVATION; PHENOTYPE; HEIGHT; FAMILY; LENGTH},
language = {eng},
issn = {0804-4643},
journal = {European Journal od Endocrinology},
title = {A novel variant of FGFR3 causes proportionate short stature},
url = {http://www.eje-online.org/content/172/6/763},
volume = {172},
year = {2015}
}
TY - JOUR
ID - 1306875
AU - Kant, Sarina G. - Červenková, Iveta - Bálek, Lukáš - Trantírek, Lukáš - Santen, Gijs W. E. - Vries, Martine C. de - Duyvenvoorde, Hermine A. van - Wielen, Michiel J. R. van der - Verkerk, Annemieke J. M. H. - Uitterlinden, André G. - Hannema, Sabine E. - Wit, Jan M. - Oostdijk, Wilma - Krejčí, Pavel - Losekoot, Monique
PY - 2015
TI - A novel variant of FGFR3 causes proportionate short stature
JF - European Journal od Endocrinology
VL - 172
IS - 6
SP - 763-770
EP - 763-770
PB - Bioscientifica LTD
SN - 08044643
KW - FACTOR RECEPTOR-3 GENE
KW - ASN540SER MUTATION
KW - DUTCH CHILDREN
KW - HYPOCHONDROPLASIA
KW - ACTIVATION
KW - PHENOTYPE
KW - HEIGHT
KW - FAMILY
KW - LENGTH
UR - http://www.eje-online.org/content/172/6/763
N2 - Objective: 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. Design: 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. Methods: 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. Results: 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 showed normal functionality in vitro compared with WT. Conclusions: Proportionate short stature can be caused by a mutation in FGFR3. Sequencing of this gene can be considered in patients with short stature, especially when there is an autosomal dominant pattern of inheritance. However, functional studies and segregation studies should be performed before concluding that a variant is pathogenic.
ER -
KANT, Sarina G., Iveta ČERVENKOVÁ, Lukáš BÁLEK, Lukáš TRANTÍREK, Gijs W. E. SANTEN, Martine C. de VRIES, Hermine A. van DUYVENVOORDE, Michiel J. R. van der WIELEN, Annemieke J. M. H. VERKERK, André G. UITTERLINDEN, Sabine E. HANNEMA, Jan M. WIT, Wilma OOSTDIJK, Pavel KREJČÍ a Monique LOSEKOOT. A novel variant of FGFR3 causes proportionate short stature. \textit{European Journal od Endocrinology}. Bristol: Bioscientifica LTD, 2015, roč.~172, č.~6, s.~763-770. ISSN~0804-4643. doi:10.1530/EJE-14-0945.
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