(2007) identified a chromosome 7 uniparental isodisomy and a 7p telomeric microdeletion.The extent of the deleted region at the 7p telomere was established by genotyping microsatellite markers across the telomeric region. Sequence analysis of FAM20C, located within the deleted region, in 6 patients with the disorder revealed 4 homozygous and 2 compound heterozygous mutations (611061.0001-611061.0008).Northern blot analysis of mouse tissues showed highest levels of transcript in the dental pulp-odontoblast complex, moderate expression in bone, and low expression in kidney, liver, brain, and lung.
Fam20c -/- mice showed widespread reduced bone mineral content and density, total or near total lack of dental enamel, and endodontal and periodontal inflammation.FAM20C phosphorylates the caseins and several secreted proteins implicated in biomineralization, including the small integrin-binding ligand N-linked glycoproteins (SIBLINGs).This explains why mutations in FAM20C cause an osteosclerotic bone dysplasia in humans known as Raine syndrome (259775). (2005) identified a family of genes with related sequence that included 2 additional members in mammals, FAM20B (611063) and FAM20C.The 3 deduced proteins are highly conserved in human, mouse, and rat.The FAM20C mutants phosphorylated OPN less efficiently than the wildtype.Most mutations prevented FAM20C secretion, despite the fact that many localized within the secretory pathway.Bone of Fam20c -/- mice showed thickened and disorganized growth plate cartilage at 4 and 14 weeks of age.Spongiosa had disorganized capillaries, osteoblasts, and osteoid, and osteoclasts were smaller than normal.(2009) noted that these mutations were not shared with any of the previously reported mutation-positive patients who died in infancy, suggesting that these mutations might confer a milder phenotype.In 2 sisters, born of first-cousin parents of Algerian origin, who had an attenuated phenotype of Raine syndrome with normal psychomotor development at ages 4 years and 1 year, respectively, 20825432] [Full Text]" pmid="20825432" Wang et al.