Bent Bone Dysplasia-FGFR2 type, a Distinct Skeletal Disorder,
Has Deficient Canonical FGF Signaling

J 2012

Bent Bone Dysplasia-FGFR2 type, a Distinct Skeletal Disorder, Has Deficient Canonical FGF Signaling

MERRILL, A.E., A. SARUKHANOV, Pavel KREJČÍ, B. IDONI, N. CAMACHO et. al.

Základní údaje

Originální název

Bent Bone Dysplasia-FGFR2 type, a Distinct Skeletal Disorder, Has Deficient Canonical FGF Signaling

Autoři

MERRILL, A.E. (840 Spojené státy), A. SARUKHANOV (840 Spojené státy), Pavel KREJČÍ (203 Česká republika, garant, domácí), B. IDONI (840 Spojené státy), N. CAMACHO (840 Spojené státy), K.D. ESTRADA (840 Spojené státy), K.M. LYONS (840 Spojené státy), H. DEIXLER (840 Spojené státy), H. ROBINSON (840 Spojené státy), D. CHITAYAT (840 Spojené státy), C.J. CURRY (840 Spojené státy), R.S. LACHMAN (840 Spojené státy), W.R. WILCOX (840 Spojené státy) a D. KRAKOW (840 Spojené státy)

Vydání

The American Journal of Human Genetics, Chicago, University of Chicago Press, 2012, 0002-9297

Další údaje

Jazyk

angličtina

Typ výsledku

Článek v odborném periodiku

Obor

30105 Physiology

Stát vydavatele

Spojené státy

Utajení

není předmětem státního či obchodního tajemství

Impakt faktor

Impact factor: 11.202

Kód RIV

RIV/00216224:14310/12:00059827

Organizační jednotka

Přírodovědecká fakulta

DOI

http://dx.doi.org/10.1016/j.ajhg.2012.02.005

UT WoS

000301762800022

Klíčová slova anglicky

APERT-SYNDROME; LADD SYNDROME; GROWTH; MUTATIONS; RECEPTOR-2; ACTIVATION; INDUCTION; CROUZON; MOUSE; DISRUPTION

Štítky

AKR, rivok

Změněno: 9. 4. 2013 13:41, Ing. Andrea Mikešková

Anotace

V originále

Fibroblast growth factor receptor 2 (FGFR2) is a crucial regulator of bone formation during embryonic development. Both gain and loss-of-function studies in mice have shown that FGFR2 maintains a critical balance between the proliferation and differentiation of osteoprogenitor cells. We have identified de novo FGFR2 mutations in a sporadically occurring perinatal lethal skeletal dysplasia characterized by poor mineralization of the calvarium, craniosynostosis, dysmorphic facial features, prenatal teeth, hypoplastic pubis and clavicles, osteopenia, and bent long bones. Histological analysis of the long bones revealed that the growth plate contained smaller hypertrophic chondrocytes and a thickened hypercellular periosteum. Four unrelated affected individuals were found to be heterozygous for missense mutations that introduce a polar amino acid into the hydrophobic transmembrane domain of FGFR2. Using diseased chondrocytes and a cell-based assay, we determined that these mutations selectively reduced plasma-membrane levels of FGFR2 and markedly diminished the receptor's responsiveness to extracellular FGF. All together, these clinical and molecular findings are separate from previously characterized FGFR2 disorders and represent a distinct skeletal dysplasia.

Návaznosti

MUNI/A/0975/2009, interní kód MU

Název: Podpora výzkumné činnosti studentů v oblasti fyziologie a imunologie živočichů. (Akronym: VYFIŽ)

Investor: Masarykova univerzita, Podpora výzkumné činnosti studentů v oblasti fyziologie a imunologie živočichů., DO R. 2020_Kategorie A - Specifický výzkum - Studentské výzkumné projekty

Citovat

MERRILL, A.E., A. SARUKHANOV, Pavel KREJČÍ, B. IDONI, N. CAMACHO, K.D. ESTRADA, K.M. LYONS, H. DEIXLER, H. ROBINSON, D. CHITAYAT, C.J. CURRY, R.S. LACHMAN, W.R. WILCOX a D. KRAKOW. Bent Bone Dysplasia-FGFR2 type, a Distinct Skeletal Disorder, Has Deficient Canonical FGF Signaling. The American Journal of Human Genetics. Chicago: University of Chicago Press, 2012, roč. 90, č. 3, s. 550-557. ISSN 0002-9297. Dostupné z: https://dx.doi.org/10.1016/j.ajhg.2012.02.005.

@article{980985,
   author = {Merrill, A.E. and Sarukhanov, A. and Krejčí, Pavel and Idoni, B. and Camacho, N. and Estrada, K.D. and Lyons, K.M. and Deixler, H. and Robinson, H. and Chitayat, D. and Curry, C.J. and Lachman, R.S. and Wilcox, W.R. and Krakow, D.},
   article_location = {Chicago},
   article_number = {3},
   doi = {http://dx.doi.org/10.1016/j.ajhg.2012.02.005},
   keywords = {APERT-SYNDROME; LADD SYNDROME; GROWTH; MUTATIONS; RECEPTOR-2; ACTIVATION; INDUCTION; CROUZON; MOUSE; DISRUPTION},
   language = {eng},
   issn = {0002-9297},
   journal = {The American Journal of Human Genetics},
   title = {Bent Bone Dysplasia-FGFR2 type, a Distinct Skeletal Disorder, Has Deficient Canonical FGF Signaling},
   volume = {90},
   year = {2012}
}

TY  - JOUR
ID  - 980985
AU  - Merrill, A.E. - Sarukhanov, A. - Krejčí, Pavel - Idoni, B. - Camacho, N. - Estrada, K.D. - Lyons, K.M. - Deixler, H. - Robinson, H. - Chitayat, D. - Curry, C.J. - Lachman, R.S. - Wilcox, W.R. - Krakow, D.
PY  - 2012
TI  - Bent Bone Dysplasia-FGFR2 type, a Distinct Skeletal Disorder, Has Deficient Canonical FGF Signaling
JF  - The American Journal of Human Genetics
VL  - 90
IS  - 3
SP  - 550-557
EP  - 550-557
PB  - University of Chicago Press
SN  - 00029297
KW  - APERT-SYNDROME
KW  - LADD SYNDROME
KW  - GROWTH
KW  - MUTATIONS
KW  - RECEPTOR-2
KW  - ACTIVATION
KW  - INDUCTION
KW  - CROUZON
KW  - MOUSE
KW  - DISRUPTION
N2  - Fibroblast growth factor receptor 2 (FGFR2) is a crucial regulator of bone formation during embryonic development. Both gain and loss-of-function studies in mice have shown that FGFR2 maintains a critical balance between the proliferation and differentiation of osteoprogenitor cells. We have identified de novo FGFR2 mutations in a sporadically occurring perinatal lethal skeletal dysplasia characterized by poor mineralization of the calvarium, craniosynostosis, dysmorphic facial features, prenatal teeth, hypoplastic pubis and clavicles, osteopenia, and bent long bones. Histological analysis of the long bones revealed that the growth plate contained smaller hypertrophic chondrocytes and a thickened hypercellular periosteum. Four unrelated affected individuals were found to be heterozygous for missense mutations that introduce a polar amino acid into the hydrophobic transmembrane domain of FGFR2. Using diseased chondrocytes and a cell-based assay, we determined that these mutations selectively reduced plasma-membrane levels of FGFR2 and markedly diminished the receptor's responsiveness to extracellular FGF. All together, these clinical and molecular findings are separate from previously characterized FGFR2 disorders and represent a distinct skeletal dysplasia.
ER  -

MERRILL, A.E., A. SARUKHANOV, Pavel KREJČÍ, B. IDONI, N. CAMACHO, K.D. ESTRADA, K.M. LYONS, H. DEIXLER, H. ROBINSON, D. CHITAYAT, C.J. CURRY, R.S. LACHMAN, W.R. WILCOX a D. KRAKOW. Bent Bone Dysplasia-FGFR2 type, a Distinct Skeletal Disorder, Has Deficient Canonical FGF Signaling. \textit{The American Journal of Human Genetics}. Chicago: University of Chicago Press, 2012, roč.~90, č.~3, s.~550-557. ISSN~0002-9297. Dostupné z: https://dx.doi.org/10.1016/j.ajhg.2012.02.005.

Podrobný výpis o publikaci