A Point Mutation in PDGFRB Causes Autosomal-Dominant Penttinen Syndrome.
Am J Hum Genet
; 97(3): 465-74, 2015 Sep 03.
Article
en En
| MEDLINE
| ID: mdl-26279204
ABSTRACT
Penttinen syndrome is a distinctive disorder characterized by a prematurely aged appearance with lipoatrophy, epidermal and dermal atrophy along with hypertrophic lesions that resemble scars, thin hair, proptosis, underdeveloped cheekbones, and marked acro-osteolysis. All individuals have been simplex cases. Exome sequencing of an affected individual identified a de novo c.1994T>C p.Val665Ala variant in PDGFRB, which encodes the platelet-derived growth factor receptor ß. Three additional unrelated individuals with this condition were shown to have the identical variant in PDGFRB. Distinct mutations in PDGFRB have been shown to cause infantile myofibromatosis, idiopathic basal ganglia calcification, and an overgrowth disorder with dysmorphic facies and psychosis, none of which overlaps with the clinical findings in Penttinen syndrome. We evaluated the functional consequence of this causative variant on the PDGFRB signaling pathway by transfecting mutant and wild-type cDNA into HeLa cells, and transfection showed ligand-independent constitutive signaling through STAT3 and PLCγ. Penttinen syndrome is a clinically distinct genetic condition caused by a PDGFRB gain-of-function mutation that is associated with a specific and unusual perturbation of receptor function.
Texto completo:
1
Colección:
01-internacional
Banco de datos:
MEDLINE
Asunto principal:
Progeria
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Transducción de Señal
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Mutación Puntual
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Deformidades Congénitas de las Extremidades
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Receptor beta de Factor de Crecimiento Derivado de Plaquetas
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Acroosteólisis
Tipo de estudio:
Etiology_studies
/
Prognostic_studies
Límite:
Female
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Humans
/
Male
Idioma:
En
Revista:
Am J Hum Genet
Año:
2015
Tipo del documento:
Article
País de afiliación:
Estados Unidos