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| Intellectual disability - microarray and sequencing v2.813 | TELO2 | Rebecca Foulger Classified gene: TELO2 as Green List (high evidence) | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Intellectual disability - microarray and sequencing v2.813 | TELO2 | Rebecca Foulger Added comment: Comment on list classification: TELO2 was added to the ID panel by Konstantinos Varvagiannis, and rated Green. Updated rating from Grey to Green based on the evidence Konstantinos provides. In summary, PMID:27132593 (You et al., 2016) report six individuals from 4 families with syndromic ID and compound het variants in TELO2. PMID:28944240 (Moosa et al., 2017) report a family with two sisters harbouring compound het TEL02 variants and with dysmorphic features. The surviving sister had severe ID and global DD in addition to the dysmorphism. Therefore sufficient cases to support association with You-Hoover-Fong syndrome (MIM:616954), which has a spectrum of phenotypes but includes intellectual disability as a consistent feature. | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Intellectual disability - microarray and sequencing v2.813 | TELO2 | Rebecca Foulger Gene: telo2 has been classified as Green List (High Evidence). | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Intellectual disability - microarray and sequencing v2.812 | TELO2 | Rebecca Foulger Phenotypes for gene: TELO2 were changed from You-Hoover-Fong syndrome, MIM 616954 to You-Hoover-Fong syndrome, 616954, syndromic intellectual disability | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Intellectual disability - microarray and sequencing v2.555 | TELO2 |
Konstantinos Varvagiannis gene: TELO2 was added gene: TELO2 was added to Intellectual disability. Sources: Literature,Expert Review Mode of inheritance for gene: TELO2 was set to BIALLELIC, autosomal or pseudoautosomal Publications for gene: TELO2 were set to 27132593; 28944240 Phenotypes for gene: TELO2 were set to You-Hoover-Fong syndrome, MIM 616954 Penetrance for gene: TELO2 were set to Complete Review for gene: TELO2 was set to GREEN gene: TELO2 was marked as current diagnostic Added comment: 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. As a result heterozygosity for the complex variant may be confounded with compound heterozygous state until segregation studies are performed. 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 (of ID, dwarfism, retinitis pigmentosa, etc) compared to previously reported patients. // Biallelic mutations in TTI2 (of the same complex) lead to similar phenotypes (gene rated green in the ID panel). // TELO2 is included in gene panels for intellectual disability offered by different diagnostic laboratories. // As a result this gene can be considered for inclusion in this panel as green. Sources: Literature, Expert Review |
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