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Skeletal dysplasia

Gene: TONSL

Amber List (moderate evidence)

TONSL (tonsoku like, DNA repair protein)
EnsemblGeneIds (GRCh38): ENSG00000160949
EnsemblGeneIds (GRCh37): ENSG00000160949
OMIM: 604546, Gene2Phenotype
TONSL is in 1 panel

2 reviews

Michael Oldridge (NHS)

Green List (high evidence)

multiple unrelated patients described with recessive LOF mutations.
Created: 31 Jan 2021, 4:52 p.m. | Last Modified: 31 Jan 2021, 4:52 p.m.
Panel Version: 2.80

Mode of inheritance
BIALLELIC, autosomal or pseudoautosomal

Phenotypes
SPONASTRIME dysplasia

Publications

Eleanor Williams (Genomics England Curator)

Green List (high evidence)

Comment on list classification: updating from red to amber, but with a recommendation for green rating at the next GMS review.
Created: 2 Dec 2020, 5:45 p.m. | Last Modified: 2 Dec 2020, 5:45 p.m.
Panel Version: 2.34
Associated with Spondyloepimetaphyseal dysplasia, sponastrime type MIM#271510 (AR) in OMIM.

PMID: 30773277 - Burrage et al 2019 - identified, using WES or Sanger sequencing, compound heterozygous variants in TONSL in 9 individuals (8 families) with SPONASTRIME dysplasia. 4 other probands with SPONASTRIME dysplasia did not have biallelic variants in TONSL or in MMS22L, but two of them did have a single heterozygous variants in TONSL. The authors say they cannot exclude deep intronic, promotor variants or large intragenic rearrangements/deletions in these patients. An additional 4 individuals (3 families) with short stature of varied severity and spondylometaphyseal dysplasia with or without immunologic and hematologic abnormalities were also found to have compound heterozygous variants in TONSL.

PMID: 30773278 - Chang et al 2019 - Using WES they identified homozygous or compound heterozygous TONSL variants in 10 of 13 individuals (9 families) with SPONASTRIME dysplasia.

PMID: 32959051 - Micale et al 2020 - report a 9-year-old Italian girl with typical SPONASTRIME dysplasia who was found to have two novel missense variants in TONSL. Each parent was heterozygous for one of the variants. Both variants were found to be very rare in the gnomad database. Patient-derived fibroblasts show increased levels of spontaneous chromosomal breaks, reduced cell proliferation and enhanced apoptosis.
Sources: Literature
Created: 2 Dec 2020, 5:44 p.m.

Mode of inheritance
BIALLELIC, autosomal or pseudoautosomal

Phenotypes
Spondyloepimetaphyseal dysplasia, sponastrime type OMIM:271510; spondyloepimetaphyseal dysplasia, sponastrime type MONDO:0010068

Publications

Details

Mode of Inheritance
BIALLELIC, autosomal or pseudoautosomal
Sources
  • Expert Review Amber
  • Literature
Phenotypes
  • Spondyloepimetaphyseal dysplasia, sponastrime type OMIM:271510
  • spondyloepimetaphyseal dysplasia, sponastrime type MONDO:0010068
Tags
for-review
OMIM
604546
Clinvar variants
Variants in TONSL
Penetrance
None
Publications
Panels with this gene

History Filter Activity

2 Dec 2020, Gel status: 2

Entity classified by Genomics England curator

Eleanor Williams (Genomics England Curator)

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

2 Dec 2020, Gel status: 1

Added Tag

Eleanor Williams (Genomics England Curator)

Tag for-review tag was added to gene: TONSL.

2 Dec 2020, Gel status: 1

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

Eleanor Williams (Genomics England Curator)

gene: TONSL was added gene: TONSL was added to Skeletal dysplasia. Sources: Literature Mode of inheritance for gene: TONSL was set to BIALLELIC, autosomal or pseudoautosomal Publications for gene: TONSL were set to 32959051; 30773278; 30773277 Phenotypes for gene: TONSL were set to Spondyloepimetaphyseal dysplasia, sponastrime type OMIM:271510; spondyloepimetaphyseal dysplasia, sponastrime type MONDO:0010068 Review for gene: TONSL was set to GREEN