Severe microcephaly

Gene: TRAPPC12

The rating of this gene has been updated following NHS Genomic Medicine Service approval.

Created: 10 Mar 2022, 10:52 a.m. | Last Modified: 10 Mar 2022, 10:52 a.m.

Panel Version: 2.282

Green List (high evidence)

Comment on list classification: There is enough evidence to rate this gene Green at the next GMS panel update (added 'for-review' tag) - sufficient unrelated published cases, plus an internally diagnosed individual; where measurements were indicated (3/5 cases), microcephaly was of relevant severity to this panel (<−3 SD)

Created: 20 Jan 2021, 5:16 p.m. | Last Modified: 20 Jan 2021, 5:16 p.m.

Panel Version: 2.73

- 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.
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.

- PMID: 32369837 (2020) - Two unrelated patients with severe neurodevelopmental delay and brain atrophy, and different homozygous variants in this gene. One individual also presented epilepsy and microcephaly (-5.72 SD).

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Copied from Intellectual disability panel review by Louise Daugherty (Genomics England Curator), 1 Jul 2019:

"in addition to this published evidence, recently a diagnosis of TRAPPC12 from an exome has been discovered (pers. comm Genomics England clinical team), however the case had a negative 100K Genomes Project report, as there was not enough evidence to make the gene Green at the time. The child had developmental delay, microcephaly and cerebellar hypoplasia"

Created: 20 Jan 2021, 5:11 p.m. | Last Modified: 20 Jan 2021, 5:11 p.m.

Panel Version: 2.72

Phenotypes
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

• 28777934
• 32369837

Green List (high evidence)

Four families reported with a severe progressive encephalopathy characterized by microcephaly, global developmental delay, and hearing loss.
Sources: Expert list

Created: 4 Sep 2020, 2:32 a.m.

Mode of inheritance
BIALLELIC, autosomal or pseudoautosomal

Phenotypes
Encephalopathy, progressive, early-onset, with brain atrophy and spasticity, MIM# 617669

Publications

• 32369837
• 28777934

Variants in this GENE are reported as part of current diagnostic practice