The Gene for Autosomal Dominant Craniometaphyseal Dysplasia Maps to Chromosome 5p and Is Distinct from the Growth Hormone-Receptor Gene

• Published in: American journal of human genetics Vol. 61; no. 4; pp. 918 - 923
• Main Authors: Nürnberg, Peter, Tinschert, Sigrid, Mrug, Michal, Hampe, Jochen, Müller, Clemens R., Fuhrmann, Eike, Braun, Hans-Steffen, Reis, André
• Format: Journal Article
• Language: English
• Published: Chicago, IL Elsevier Inc 01.10.1997; University of Chicago Press
• Subjects: Biological and medical sciences; Chromosome Mapping; Chromosomes, Human, Pair 5; Craniofacial Abnormalities - genetics; Diseases of the osteoarticular system; Facial Bones - abnormalities; Female; Genes, Dominant; Genetic Linkage; Genetic Markers; Germany; Humans; Hyperostosis - genetics; Lod Score; Male; Malformations and congenital and or hereditary diseases involving bones. Joint deformations; Medical sciences; Microsatellite Repeats; Pedigree; Receptors, Somatotropin - genetics; Sclerosis - genetics; Skull - abnormalities; Germany; Genetic mapping; Human; Short arm; Genetic inheritance; Family study; STH; Diseases of the osteoarticular system; Chromosome B5; Genetic disease; Craniometaphyseal dysplasia; Genetics; Dominant character; Locus; Osteochondrodysplasia; Hormonal receptor
• ISSN: 0002-9297; 1537-6605
• DOI: 10.1086/514880

Craniometaphyseal dysplasia (CMD) is an osteochon-drodysplasia of unknown etiology characterized by hy-perostosis and sclerosis of the craniofacial bones associated with abnormal modeling of the metaphyses. Sclerosis of the skull may lead to asymmetry of the mandible, as well as to cranial nerve compression, that finally may result in hearing loss and facial palsy. We have analyzed a large German kindred with autosomal dominant (AD) CMD and found tight linkage between the disorder and microsatellite markers on chromosome 5p (maximum two-point LOD score 4.82; θ = 0). Our results clearly establish the existence of a locus for AD CMD on central chromosome 5p (5p15.2–p14.1). This region overlaps with the mapping interval of the growth hormone—receptor (GHR) gene (5p14–p12), which is known to be involved in the mitogenic activation of osteoblasts. Therefore, we tested the GHR gene as a candidate gene. However, recombination events between the CMD locus and the GHR gene identified in two members of this family clearly exclude this candidate.