Medizinische Universität Graz Austria/Österreich - Forschungsportal - Medical University of Graz

Logo MUG-Forschungsportal

Gewählte Publikation:

SHR Neuro Krebs Kardio Lipid

Muhn, F; Klopocki, E; Graul-Neumann, L; Uhrig, S; Colley, A; Castori, M; Lankes, E; Henn, W; Gruber-Sedlmayr, U; Seifert, W; Horn, D.
Novel mutations of the PRKAR1A gene in patients with acrodysostosis.
Clin Genet. 2013; 84(6):531-538
Web of Science PubMed FullText FullText_MUG

 

Autor/innen der Med Uni Graz:
Gruber-Sedlmayr Ursula
Uhrig Sabine
Gendermonitor:
Altmetrics:

Abstract:
Acrodysostosis is characterized by a peripheral dysostosis that is accompanied by short stature, midface hypoplasia, and developmental delay. Recently, it was shown that heterozygous point mutations in the PRKAR1A gene cause acrodysostosis with hormone resistance. By mutational analysis of the PRKAR1A gene we detected four different mutations (p.Arg368Stop, p.Ala213Thr, p.Tyr373Cys, and p.Arg335Cys) in four of seven affected patients with acrodysostosis. The combination of clinical results, endocrinological parameters and in silico mutation analysis gives evidence to suppose a pathogenic effect of each mutation. This assumption is supported by the de novo origin of these mutations. Apart from typical radiological abnormalities of the hand bones, elevated thyroid stimulating hormone and parathyroid hormone values as well as short stature are the most common findings. Less frequent features are characteristic facial dysmorphisms, sensorineural hearing loss and mild intellectual disability. These results lead to the conclusion that mutations of PKRAR1A are the major molecular cause for acrodysostosis with endocrinological abnormalities. In addition, in our cohort of 44 patients affected with brachydactyly type E (BDE) we detected only one sequence variant of PRKAR1A (p.Asp227Asn) with an unclear effect on protein function. Thus, we conclude that PRKAR1A mutations may play no major role in the pathogenesis of BDE. © 2013 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.
Find related publications in this database (using NLM MeSH Indexing)
Adolescent -
Adult -
Alleles -
Child -
Cyclic AMP-Dependent Protein Kinase RIalpha Subunit - genetics
DNA Mutational Analysis -
Dysostoses - diagnosis
Female -
Hand Bones - pathology
Humans -
Intellectual Disability - diagnosis
Male -
Mutation -
Osteochondrodysplasias - diagnosis
Phenotype -
Young Adult -

Find related publications in this database (Keywords)
acrodysostosis
brachydactyly type E
PRKAR1A
protein kinase A regulatory subunit I alpha
© Meduni Graz Impressum