Amelogenesis imperfecta
Gene: FAM20CComment when marking as ready: Marked as ready: October 18th 2017.Created: 18 Oct 2017, 11:59 a.m.
Comment on list classification: Updated rating from Red to Green: Expert green review plus FAM20C is on 'prior genetic testing' inclusion list. Confirmed DD-G2P gene for 'Raine syndrome' which (when non-lethal) can present with AI. Sufficient cases (at least 3) of Raine syndrome with AI (PMIDs:25928877 and 27667191) to support causation.Created: 18 Oct 2017, 11:58 a.m.
PMID:27667191 (2016) report a consanguineous Moroccan family with 2 siblings affected with Raine syndrome and features include learning disability, seizures and AI. A homozygous variant 676T>A (Trp226Arg) was identified in the affected siblings.Created: 18 Oct 2017, 11:55 a.m.
PMID:25928877 (Acevedo et al., 2015) report 5 individuals from 2 consanguineous Brazilian families with Raine syndrome and AI phenotypes. Family 1 included 3 siblings with hypoplastic Amelogenesis Imperfecta (inherited abnormal dental enamel formation): A homozygous FAM20C donor splice site mutation (c.784+5g>c) was identified. Family 2 included 2 siblings with hypoplastic AI and tooth dentine abnormalities as part of a more obvious syndrome with facial dysmorphism: A homozygous missense mutation in FAM20C (c.1487C > T; p.P496L) was identified.Created: 8 Jun 2017, 10:37 a.m.
Biallelic mutations in FAM20C were originally identified in natal or perinatal lethal cases of Raine syndrome. Raine syndrome is a neonatal osteosclerotic bone dysplasia with characteristic facial features with exophthalmos. However some variants do not lead to a lethal phenotype and children survive beyond the appearance of teeth. In these patients, amelogenesis imperfecta, hearing loss, seizures, and intracerebral calcification are apparent. The variation in the lethality of FAM20C variants has been summarised as "Individuals with nonsense or frameshift mutations or missense variants in the conserved C-terminal domain (CCD), which has kinase activity, consistent with a null phenotype do not survive the newborn period. In contrast, the attenuated form of Raine syndrome is due to hypomorphic FAM20C alleles and has been associated with raised FGF23 levels (Rafaelsen et al., 2013 and Takeyari et al., 2014)" see Elalaoui, 2016. The individuals surviving to later childhood have hypoplastic AI. Over 20 different variants have been associated with lethal or non-lethal Raine syndrome, this includes large genomic rearrangements including duplications, as well as missense and splicing variants.Created: 18 Sep 2017, 3:56 p.m.
Mode of inheritance
BIALLELIC, autosomal or pseudoautosomal
Phenotypes
OMIM:259775 Raine Syndrome
Publications
This panel has been promoted after review by Claire Smith (Leeds) and further personal consultation with Dr Smith
This gene has been classified as Green List (High Evidence).
This gene has been classified as Green List (High Evidence).
This gene has been classified as Red List (Low Evidence).
Publications for FAM20C were set to 25928877; 17924334; 24039075; 24458843; 19250384; 23325605; 20825432; 24982027; 20453638; 27667191; 27862258
Phenotypes for FAM20C were set to Raine Syndrome, 259775; hypoplastic Amelogenesis Imperfecta
Publications for FAM20C were set to 25928877
Phenotypes for FAM20C were set to Raine Syndrome, 259775
Phenotypes for FAM20C were set to Raine Syndrome, 259775
Publications for FAM20C were set to 26740946
FAM20C was added to Amelogenesis Imperfectapanel. Source: UKGTN Model of inheritance for gene FAM20C was set to BIALLELIC, autosomal or pseudoautosomal
FAM20C was added to Amelogenesis Imperfectapanel. Sources: Eligibility statement prior genetic testing
FAM20C was created by rfoulger