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| Intellectual disability v6.11 | TTI1 | Achchuthan Shanmugasundram Tag Q3_23_promote_green was removed from gene: TTI1. | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Intellectual disability v6.11 | TTI1 | Sarah Leigh commented on gene: TTI1: The rating of this gene has been updated to Green and the mode of inheritance set to BIALLELIC, autosomal or pseudoautosomal following NHS Genomic Medicine Service approval. | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Intellectual disability v6.10 | TTI1 |
Achchuthan Shanmugasundram Source Expert Review Green was added to TTI1. Source NHS GMS was added to TTI1. Rating Changed from Amber List (moderate evidence) to Green List (high evidence) |
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| Intellectual disability v6.8 | TTI1 | Arina Puzriakova Added comment: Comment on phenotypes: Relevant phenotype now listed in OMIM (Neurodevelopmental disorder with microcephaly and movement abnormalities, OMIM:620445) | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Intellectual disability v6.8 | TTI1 | Arina Puzriakova Phenotypes for gene: TTI1 were changed from neurodevelopmental disorder with microcephaly to Neurodevelopmental disorder with microcephaly and movement abnormalities, OMIM:620445 | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Intellectual disability v5.189 | TTI1 | Sarah Leigh Classified gene: TTI1 as Amber List (moderate evidence) | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Intellectual disability v5.189 | TTI1 | Sarah Leigh Added comment: Comment on list classification: There is enough evidence for this gene to be rated GREEN at the next major review. | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Intellectual disability v5.189 | TTI1 | Sarah Leigh Gene: tti1 has been classified as Amber List (Moderate Evidence). | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Intellectual disability v5.188 | TTI1 | Sarah Leigh Tag Q3_23_promote_green tag was added to gene: TTI1. | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Intellectual disability v5.188 | TTI1 |
Sarah Leigh gene: TTI1 was added gene: TTI1 was added to Intellectual disability - microarray and sequencing. Sources: Literature Mode of inheritance for gene: TTI1 was set to BIALLELIC, autosomal or pseudoautosomal Publications for gene: TTI1 were set to 36724785 Phenotypes for gene: TTI1 were set to neurodevelopmental disorder with microcephaly Review for gene: TTI1 was set to GREEN Added comment: TTI1 has not previously been associated with a phenotype in OMIM, Gen2Phen or MONDO. At least 2 variants have been reported. PMID: 36724785 reported 15 TTI1 variants as either homozygotes (2 families) or compound heterozygotes (7 families) in cases with a neurodevelopmental disorder with microcephaly. In all cases the parents were heterozygous carriers of the TTI1 variant identified in the affected child. Development delay was observed in all of the families (9/9), moderate to severe intellectual disability was evident in all families where it could be assessed (8/8) and severe microcephaly was present in members of 5/9 families. Supportive functional results were also presented. Sources: Literature |
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| Intellectual disability 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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