Ataxia and cerebellar anomalies - narrow panel
Gene: MTCL1
The rating of this gene has been updated to green following NHS Genomic Medicine Service approval.Created: 5 Feb 2023, 5:18 p.m. | Last Modified: 5 Feb 2023, 5:18 p.m.
Panel Version: 3.30
Comment on list classification: New gene added by Zornitza Stark. There is sufficient evidence to promote this gene to Green at the next GMS panel update - two unrelated individuals with different LoF variants in this gene. Ataxia with cerebellar atrophy was the predominant presentation in both cases (PMIDs: 30548255; 32961396). Knockout animal model recapitulates human phenotypes and provides functional support.Created: 13 May 2021, 10:27 a.m. | Last Modified: 13 May 2021, 10:27 a.m.
Panel Version: 2.175
- PMID: 30548255 (2019) - Homozygous MTCL1 truncating variant (c.1219delA; p.Lys407fs) was identified in a 23-year-old Polish patient with slowly progressive cerebellar ataxia, mild ID, seizures in childhood and episodic pain in the lower limbs triggered by physical exertion. Unaffected parents and sib were heterozygous carriers.
- PMID: 32961396 (2020) - Single individual with cerebellar ataxia, ID, spastic gait, dysarthria, intentional tremor, increased muscle tension and a homozygous nonsense variant (c.121G>T, p.E41*) in MTCL1.
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MTCL1 encodes a microtubule-associated protein highly expressed in cerebellar Purkinje cells and is crucial for maintaining Purkinje neuron axon initial segment. Mtcl1 knockout mice exhibit abnormal motor coordination due to axonal degeneration and Purkinje cell loss (PMID: 28283581)Created: 13 May 2021, 10:21 a.m. | Last Modified: 13 May 2021, 10:21 a.m.
Panel Version: 2.174
Mode of inheritance
BIALLELIC, autosomal or pseudoautosomal
Phenotypes
Cerebellar ataxia
Publications
Two families reported with bi-allelic LOF variants, early onset ataxia and a supportive null mouse model.
Single family with mono-allelic variant in two individuals and adult-onset ataxia (not pertinent to this panel, and less compelling).
Sources: LiteratureCreated: 9 Dec 2020, 6:19 a.m.
Mode of inheritance
BIALLELIC, autosomal or pseudoautosomal
Phenotypes
slowly progressive cerebellar ataxia; mild intellectual disability; seizures; episodic pain; spinocerebellar ataxia
Publications
Tag gene-checked tag was added to gene: MTCL1.
Tag Q2_21_rating was removed from gene: MTCL1.
Source Expert Review Green was added to MTCL1. Source NHS GMS was added to MTCL1. Rating Changed from Amber List (moderate evidence) to Green List (high evidence)
Gene: mtcl1 has been classified as Amber List (Moderate Evidence).
Tag Q2_21_rating tag was added to gene: MTCL1.
gene: MTCL1 was added gene: MTCL1 was added to Ataxia and cerebellar anomalies - narrow panel. Sources: Literature Mode of inheritance for gene: MTCL1 was set to BIALLELIC, autosomal or pseudoautosomal Publications for gene: MTCL1 were set to 30548255; 28283581; 32961396 Phenotypes for gene: MTCL1 were set to slowly progressive cerebellar ataxia; mild intellectual disability; seizures; episodic pain; spinocerebellar ataxia Review for gene: MTCL1 was set to GREEN