Amelogenesis imperfecta

Gene: FAM20C

Green List (high evidence)

FAM20C (FAM20C, golgi associated secretory pathway kinase)
EnsemblGeneIds (GRCh38): ENSG00000177706
EnsemblGeneIds (GRCh37): ENSG00000177706
OMIM: 611061, Gene2Phenotype
FAM20C is in 12 panels

2 reviews

Rebecca Foulger (Genomics England curator)

Comment 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.

Claire Smith (University of Leeds)

Green List (high evidence)

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

Details

Mode of Inheritance
BIALLELIC, autosomal or pseudoautosomal
Sources
  • Expert Review Green
  • UKGTN
  • Eligibility statement prior genetic testing
Phenotypes
  • Raine Syndrome, 259775
  • hypoplastic Amelogenesis Imperfecta
OMIM
611061
Clinvar variants
Variants in FAM20C
Penetrance
Complete
Publications
Panels with this gene

History Filter Activity

2 Feb 2018, Gel status: 3

Panel promoted to version 1.0

Sarah Leigh (Genomics England Curator)

This panel has been promoted after review by Claire Smith (Leeds) and further personal consultation with Dr Smith

18 Oct 2017, Gel status: 4

Gene classified by Genomics England curator

Rebecca Foulger (Genomics England curator)

This gene has been classified as Green List (High Evidence).

18 Oct 2017, Gel status: 4

Gene classified by Genomics England curator

Rebecca Foulger (Genomics England curator)

This gene has been classified as Green List (High Evidence).

18 Oct 2017, Gel status: 1

Gene classified by Genomics England curator

Rebecca Foulger (Genomics England curator)

This gene has been classified as Red List (Low Evidence).

18 Oct 2017, Gel status: 1

Set publications

Rebecca Foulger (Genomics England curator)

Publications for FAM20C were set to 25928877; 17924334; 24039075; 24458843; 19250384; 23325605; 20825432; 24982027; 20453638; 27667191; 27862258

8 Jun 2017, Gel status: 1

Set Phenotypes

Rebecca Foulger (Genomics England curator)

Phenotypes for FAM20C were set to Raine Syndrome, 259775; hypoplastic Amelogenesis Imperfecta

8 Jun 2017, Gel status: 1

Set publications

Rebecca Foulger (Genomics England curator)

Publications for FAM20C were set to 25928877

8 Jun 2017, Gel status: 1

Set Phenotypes

Rebecca Foulger (Genomics England curator)

Phenotypes for FAM20C were set to Raine Syndrome, 259775

8 Jun 2017, Gel status: 1

Set Phenotypes

Rebecca Foulger (Genomics England curator)

Phenotypes for FAM20C were set to Raine Syndrome, 259775

8 Jun 2017, Gel status: 1

Set publications

Rebecca Foulger (Genomics England curator)

Publications for FAM20C were set to 26740946

8 Jun 2017, Gel status: 1

Set Mode of Inheritance, Added New Source

Rebecca Foulger (Genomics England curator)

FAM20C was added to Amelogenesis Imperfectapanel. Source: UKGTN Model of inheritance for gene FAM20C was set to BIALLELIC, autosomal or pseudoautosomal

8 Jun 2017, Gel status: 0

Added New Source

Rebecca Foulger (Genomics England curator)

FAM20C was added to Amelogenesis Imperfectapanel. Sources: Eligibility statement prior genetic testing

8 Jun 2017, Gel status: 0

Created

Rebecca Foulger (Genomics England curator)

FAM20C was created by rfoulger