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PTHR1 loss-of-function mutations in familial, nonsyndromic primary failure of tooth eruption

Official URL:https://doi.org/10.1016/j.ajhg.2008.11.006
PubMed:View item in PubMed
Creators Name:Decker, E. and Stellzig-Eisenhauer, A. and Fiebig, B.S. and Rau, C. and Kress, W. and Saar, K. and Rueschendorf, F. and Huebner, N. and Grimm, T. and Weber, B.H.
Journal Title:American Journal of Human Genetics
Journal Abbreviation:Am J Hum Genet
Volume:83
Number:6
Page Range:781-786
Date:12 December 2008
Keywords:Human Pair 3 Chromosomes, Recessive Genes, Genetic Markers, Heterozygote, Linkage, Mutation, Pedigree, Single Nucleotide Polymorphism, Parathyroid Hormone Type 1 Receptor, Tooth Eruption
Abstract:Tooth eruption is a complex developmental process requiring coordinated navigation through alveolar bone and oral epithelium. Primary failure of tooth eruption (PFE) is associated with several syndromes primarily affecting skeletal development, but it is also known as a nonsyndromic autosomal-dominant condition. Teeth in the posterior quadrants of the upper and lower jaw are preferentially affected and usually result in an open bite extending from anterior to posterior. In this study, we show that familial, nonsyndromic PFE is caused by heterozygous mutations in the gene encoding the G protein-coupled receptor for parathyroid hormone and parathyroid hormone-like hormone (PTHR1). Three distinct mutations, namely c.1050-3C > G, c.543+1G > A, and c.463G > T, were identified in 15 affected individuals from four multiplex pedigrees. All mutations truncate the mature protein and therefore should lead to a functionless receptor, strongly suggesting that haplo-insufficiency of PTHR1 is the underlying cause of nonsyndromic PFE. Although complete inactivation of PTHR1 is known to underlie the autosomal-recessive Blomstrand osteochondrodysplasia (BOCD), a lethal form of short-limbed dwarfism, our data now imply that dominantly acting PTHR1 mutations that lead to haplo-insufficiency of the receptor result in a nonsyndromic phenotype affecting tooth development with high penetrance and variable expressivity.
ISSN:0002-9297
Publisher:Cell Press / Elsevier (U.S.A.)
Item Type:Article

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