Fetal anomalies
Gene: TRAPPC12
The rating of this gene has been updated to Green following NHS Genomic Medicine Service approval.Created: 3 Mar 2022, 11:19 a.m. | Last Modified: 3 Mar 2022, 4:35 p.m.
Panel Version: 1.836
Comment on list classification: Maintaining Amber rating as currently there are not enough unrelated cases with a fetally-relevant phenotype to promote to Green. Added 'watchlist' tag.Created: 20 Jan 2021, 12:38 p.m. | Last Modified: 20 Jan 2021, 12:38 p.m.
Panel Version: 1.162
Removed 'polygenic' tag as published cases revealed no evidence to indicate polygenic inheritanceCreated: 20 Jan 2021, 12:36 p.m. | Last Modified: 20 Jan 2021, 12:36 p.m.
Panel Version: 1.158
- PMID: 32347653 (2020) - One family with recurrent fetal hydrocephalus affecting 3/4 pregnancies. Other variable anomalies included ventriculomegaly, minimal movement, and limb abnormalities (e.g. polydactyly, bilateral clubbed feet, abnormal hand positioning, short limbs). Compound het variants in the TRAPPC12 gene were identified in 2 affected fetuses, which segregated with the disorder.
- PMID: 28777934 (2017) - Three individuals from two unrelated families with severe GDD, seizures, hearing loss, microcephaly, and structural brain abnormalities including ventriculomegaly, pons hypoplasia, agenesis of the corpus callosum and brain atrophy. In family 1 (consanguineous), five previous pregnancies ended in spontaneous abortions and a sixth was terminated as a result of multiple anomalies; however, genetic analysis was not performed on these cases. In family 2, ultrasound and fetal MRI revealed agenesis of the corpus callosum but no other abnormal imaging findings in one individual.
Exome sequencing revealed different biallelic TRAPPC12 variants in both families. Patient-derived fibroblasts showed fragmentation of the Golgi, abnormal Golgi trafficking and delays in mitosis.Created: 20 Jan 2021, 12:32 p.m. | Last Modified: 20 Jan 2021, 12:32 p.m.
Panel Version: 1.158
Mode of inheritance
BIALLELIC, autosomal or pseudoautosomal
Phenotypes
Hydrocephaly; Encephalopathy, progressive, early-onset, with brain atrophy and spasticity, OMIM:617669; Early-onset progressive encephalopathy-hearing loss-pons hypoplasia-brain atrophy syndrome, MONDO:0044696
Publications
Two fetuses in one family with hydrocephaly and compound het variants. PMID: 32347653 (Gass et al 2020)
This gene is already green on other panels (Intellectual disability; Severe paediatric disorders). Here adding evidence for a fetally relevant phenotype.Created: 30 Oct 2020, 2:30 p.m. | Last Modified: 30 Oct 2020, 2:30 p.m.
Panel Version: 1.108
Mode of inheritance
BIALLELIC, autosomal or pseudoautosomal
Phenotypes
Hydrocephaly
Publications
DDG2P rating in original PAGE list: Probable for Progressive Childhood Encephalopathy and Golgi DysfunctionCreated: 11 Dec 2018, 9:05 a.m.
Polygenic tag added because MOI was listed as 'Digenic' in original PAGE file.Created: 8 Nov 2018, 4:57 p.m.
Tag watchlist was removed from gene: TRAPPC12.
Source Expert Review Green was added to TRAPPC12. Rating Changed from Amber List (moderate evidence) to Green List (high evidence)
Gene: trappc12 has been classified as Amber List (Moderate Evidence).
Publications for gene: TRAPPC12 were set to
Phenotypes for gene: TRAPPC12 were changed from Progressive Childhood Encephalopathy and Golgi Dysfunction to Hydrocephaly; Encephalopathy, progressive, early-onset, with brain atrophy and spasticity, OMIM:617669; Early-onset progressive encephalopathy-hearing loss-pons hypoplasia-brain atrophy syndrome, MONDO:0044696
Mode of inheritance for gene: TRAPPC12 was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal
Tag polygenic was removed from gene: TRAPPC12. Tag watchlist tag was added to gene: TRAPPC12.
Tag polygenic tag was added to gene: TRAPPC12.
gene: TRAPPC12 was added gene: TRAPPC12 was added to Fetal anomalies. Sources: PAGE DD-Gene2Phenotype,Expert Review Amber Mode of inheritance for gene: TRAPPC12 was set to Unknown Phenotypes for gene: TRAPPC12 were set to Progressive Childhood Encephalopathy and Golgi Dysfunction