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| Mendeliome v1.4103 | TENM4 | Bryony Thompson Classified gene: TENM4 as Amber List (moderate evidence) | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v1.4103 | TENM4 | Bryony Thompson Gene: tenm4 has been classified as Amber List (Moderate Evidence). | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v1.4102 | TENM4 |
Bryony Thompson gene: TENM4 was added gene: TENM4 was added to Mendeliome. Sources: Literature Mode of inheritance for gene: TENM4 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted Publications for gene: TENM4 were set to 41449293; 36689009; 26188006; 29249217; 34589676; 22915103 Phenotypes for gene: TENM4 were set to Neurodevelopmental disorder, MONDO:0700092; tremor, hereditary essential, 5 MONDO:0014756; first branchial cleft anomaly MONDO:0015376 Review for gene: TENM4 was set to AMBER Added comment: TENM4 encodes a type II transmembrane teneurin involved in neuronal development and oligodendrocyte maturation. Amber for essential tremor - 2 families with rare missense and supporting segregation evidence, plus mouse & zebrafish models. 2 other GDAs have limited evidence. PMID 26188006 - 3 families reported with essential tremor with incomplete segregation. 2 of the variants (p.Ala1442Thr and p.Val1138Met) are more common than expected in gnomAD. p.Thr1367Asn is a rare missense and segregates with ET over 3 generations (2 unaffected carriers under the average age of onset). Functional assays demonstrate dominant‑negative effects in oligodendrocyte precursor cells and zebrafish axon‑guidance defects for all 3 variants. PMID 36689009 - rare heterozygous missense (p.P421L) segregating in 5 affected individuals with ET in a single family PMID 29249217 - a case with hereditary tremor‑like syndrome with palatal tremor but no description of the TENM4 variant in the paper. PMID 22915103 - myelination of small-diameter axons was dramatically reduced, and differentiation of oligodendrocytes, the myelin-forming cells in the CNS, was inhibited in null mouse model. PMID 34589676 - 2 rare missense in 2 patients with first branchial cleft anomalies. No other evidence. Multiple missense in different genes in one of the patients. - limited evidence for gene-disease association PMID 41449293 - rare splice variant identified in a single family (segregates in 6 individuals) with childhood‑onset intellectual disability with epilepsy. Splice‑site‑mediated exon 10 skipping leading to seizures in a mouse model, supporting a pathogenic role. - single family reported Sources: Literature |
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