Early onset or syndromic epilepsy

Gene: TELO2

I don't know

Review and rating collated by Tracy Lester (Oxford Medical Genetics Laboratories Oxford University Hospitals NHS Foundation Trust, 2019_02_06) on behalf of Wessex and West Midlands GLH for GMS Neurology specialist test group, for Clinical Indication R59 'Early onset or syndromic epilepsy'. Review contributors: Alison Callaway and John Taylor. Suggested gene rating: Amber.

Created: 6 Aug 2019, 8:38 p.m. | Last Modified: 6 Aug 2019, 8:38 p.m.

Panel Version: 1.189

I don't know

Insufficient evidence- phenotype appears to be associated with You-Hoover-Fong syndrome, seizures do not appear to be commonly implicated in this disorder, PMID 27132593

Created: 6 Aug 2019, 8:31 p.m. | Last Modified: 6 Aug 2019, 8:31 p.m.

Panel Version: 1.188

Mode of inheritance
BIALLELIC, autosomal or pseudoautosomal

Phenotypes
You-Hoover-Fong syndrome, 616954

Publications

• 28944240

Comment when marking as ready: Associated with relevant phenotype in OMIM and as probable Gen2Phen gene. At least 7 variants reported in 7 unrelated cases, two of whome had seizures.

Created: 27 Nov 2018, 1:52 p.m.

I don't know

Biallelic mutations in TELO2 cause You-Hoover-Fong syndrome (MIM 616954). //

PMID: 27132593 reports on 6 patients (from 4 non-consanguineous families) with biallelic TELO2 variants and a similar phenotype.

Intellectual disability and microcephaly were universal features (6/6). Abnormal hearing (3/6), cortical visual impairment (3/6), abnormality of the cardiovascular system (3/6), behavioral problems (laughter outbursts in 3/6) and abnormal balance and movement disorder (6/6) were part of the phenotype. One individual had seizures.

5 missense variants and a complex allele with a stopgain variant localized in cis with a splice-site variant (NM_016111.3:c.514C>T or p.Gln172* in cis with c.2034+1G>A) are reported.

Functional studies support pathogenicity of the missense variants (reduced protein steady-state levels of TELO2 as well as TTI1 and TTI2 - the 2 other members of the TTT complex) suggesting loss of function. //

PMID: 28944240 reports on 2 sisters born to non-consanguineous parents. Both were compound heterozygous for 2 novel variants, a missense and a frameshift one. Severe microcephaly (-8.5 SD and -10.7 SD) and seizures were noted in both. The first sister passed away at the age of 2 months due to a respiratory infection. The other sister demonstrated a compatible, though much more severe phenotype (ID and microcephaly) with additional features (dwarfism, renal anomalies, retinitis pigmentosa, etc) compared to previously reported patients. //

As a result this gene could possibly be considered for inclusion in this panel as amber (seizures in 3/8 patients reported to date - these individuals belonged to 2 different families - onset may precede other manifestations of DD) .

Created: 25 Nov 2018, 4:41 p.m.

Mode of inheritance
BIALLELIC, autosomal or pseudoautosomal

Phenotypes
You-Hoover-Fong syndrome, MIM 616954

Publications

• 27132593
• 28944240