|Intellectual disability v2.718||CCDC47||Louise Daugherty Classified gene: CCDC47 as Green List (high evidence)|
|Intellectual disability v2.718||CCDC47||Louise Daugherty Added comment: Comment on list classification: New gene added by external expert and reviewed by curation team: appropriate phenotype, sufficient cases and external expert review all support gene-disease association and relevance to this panel to rate gene to Green.|
|Intellectual disability v2.718||CCDC47||Louise Daugherty Gene: ccdc47 has been classified as Green List (High Evidence).|
|Intellectual disability v2.717||CCDC47||Louise Daugherty commented on gene: CCDC47: Trichohepatoneurodevelopmental syndrome is a complex multisystem disorder characterized by woolly or coarse hair, liver dysfunction, pruritus, dysmorphic features, hypotonia, and severe global developmental delay (Morimoto el al., 2018)|
|Intellectual disability v2.717||CCDC47||Louise Daugherty Added comment: Comment on phenotypes: Added OMIM phenotype and MIMid|
|Intellectual disability v2.717||CCDC47||Louise Daugherty Phenotypes for gene: CCDC47 were changed from Woolly hair; Abnormality of the liver; Global developmental delay; Intellectual disability to Woolly hair; Abnormality of the liver; Global developmental delay; Intellectual disability; Trichohepatoneurodevelopmental syndrome, 618268|
|Intellectual disability v2.583||CCDC47||
Konstantinos Varvagiannis gene: CCDC47 was added
gene: CCDC47 was added to Intellectual disability. Sources: Literature
Mode of inheritance for gene: CCDC47 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: CCDC47 were set to 30401460
Phenotypes for gene: CCDC47 were set to Woolly hair; Abnormality of the liver; Global developmental delay; Intellectual disability
Penetrance for gene: CCDC47 were set to Complete
Review for gene: CCDC47 was set to GREEN
Added comment: Morimoto el al. (PMID: 30401460) report on 4 individuals from 4 unrelated families with biallelic LoF variants in CCDC47. The phenotype consisted of abnormal (woolly) hair, liver dysfunction, common facial features as well as DD/ID.
The patients were found to harbor the variants in compound heterozygous or more commonly in homozygous state (due to consanguinity and/or common ancestry). 4 loss-of-function variants are reported in total (using NM_020198.2 as a reference):
- c.811C>T or p.(Arg271*) [consanguineous family of Turkish origin]
- c.1145delT or p.(Leu382Argfs*2) [probably a founder mutation in Amish]
- c.1165delT or p.(Ser389Leufs*25)
- c.1189C>T or p.(Arg397*)
Decreased mRNA levels in fibroblasts/lymphoblastoid cells were shown as well as absence of the protein upon Western blot using antibodies recognizing the N and C terminus (thus suggesting NMD).
Localization of CCDC47 in the ER was demonstrated with perturbed Ca+2 homeostasis and signalling in the ER.
Ccdc47-knockout mice present features similar to the human phenotypes eg. growth, neurological as well as heart anomalies. In mice embryonic/neonatal lethality was noted in some cases which might be associated with recurrent miscarriages reported in 3 patient families.
CCDC47 is not associated with any phenotype in G2P or OMIM.
As a result, this gene can be considered for inclusion in this panel as green (or amber).