Genes in panel

Ataxia and cerebellar anomalies - narrow panel

Gene: MTCL1

Amber List (moderate evidence)

MTCL1 (microtubule crosslinking factor 1)
EnsemblGeneIds (GRCh38): ENSG00000168502
EnsemblGeneIds (GRCh37): ENSG00000168502
OMIM: 615766, Gene2Phenotype
MTCL1 is in 1 panel

2 reviews

Arina Puzriakova (Genomics England Curator)

Green List (high evidence)

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

Zornitza Stark (Australian Genomics)

Green List (high evidence)

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: Literature
Created: 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

Details

Mode of Inheritance
BIALLELIC, autosomal or pseudoautosomal
Sources
  • Expert Review Amber
Phenotypes
  • slowly progressive cerebellar ataxia
  • mild intellectual disability
  • seizures
  • episodic pain
  • spinocerebellar ataxia
Tags
Q2_21_rating
OMIM
615766
Clinvar variants
Variants in MTCL1
Penetrance
None
Publications
Panels with this gene

History Filter Activity

13 May 2021, Gel status: 2

Entity classified by Genomics England curator

Arina Puzriakova (Genomics England Curator)

Gene: mtcl1 has been classified as Amber List (Moderate Evidence).

13 May 2021, Gel status: 0

Added Tag

Arina Puzriakova (Genomics England Curator)

Tag Q2_21_rating tag was added to gene: MTCL1.

9 Dec 2020, Gel status: 0

Created, Added New Source, Set mode of inheritance, Set publications, Set Phenotypes

Zornitza Stark (Australian Genomics)

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