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Intellectual disability

Gene: DONSON

Amber List (moderate evidence)
DONSON (downstream neighbor of SON)
EnsemblGeneIds (GRCh38): ENSG00000159147
EnsemblGeneIds (GRCh37): ENSG00000159147
OMIM: 611428, Gene2Phenotype
DONSON is in 3 panels

2 reviews

Catherine Snow (Genomics England)

I don't know

Following advice from Genomics England Clinical Team DONSON will be classified as Amber. Advice was "ID is not present in all and where it is, it is reported as mild. I therefore do not think ID is likely to be the presenting feature here on the current evidence. I think the microcephaly route is more likely to pick up these families. I would rate as amber and upgrade if new evidence of more significant, or a consistent pattern, of DD/ID emerges."
Created: 24 Jun 2019, 9:12 a.m. | Last Modified: 24 Jun 2019, 9:12 a.m.
Panel Version: 0.188
Comment on list classification: Expert review by Konstantinos Varvagiannis on DONSON. At least 7 variants identified in 29 individuals from 21 families from various populations in PMIDs:28191891 and 28630177.

The most prevalent phenotype for mutations in DONSON is microcephalic dwarfism, however the features described in the table is broad as several individuals have height within the normal percentiles. Similarly, DD and more specifically ID has been observed in some patients (when it happened to be the case it was most commonly mild). No data for ID/DD was provided for 4 of the individuals and normal development was reported for 6 individuals from 4 families.

This is a borderline case as there is conflicting phenotype evidence within the variants. Therefore rating as amber and requesting feedback from clinical team.
Created: 20 May 2019, 11 a.m.
Created: 20 May 2019, 11 a.m.

Panel version: Imported from Intellectual disability update May 2019 panel version 0.188

Konstantinos Varvagiannis (Other)

I don't know

It seems that the phenotypes related to DONSON biallelic mutations (PMIDs: 28630177, 28191891) can be extremely variable with pre-/perinatally lethal cases to variable degrees of microcephaly (-2.4 to -10.7 SD), short stature (several individuals with height within the normal percentiles), limb anomalies (many without such anomalies, or at least significant). Similarly, DD and more specifically ID has been observed in some patients (when it happened to be the case it was most commonly mild).

This is most evident in the supplementary information of PMID: 28191891, specifically the following table: https://media.nature.com/original/nature-assets/ng/journal/v49/n4/extref/ng.3790-S2.xlsx

Clinical synopses for the DONSON-related phenotypes: https://www.omim.org/clinicalSynopsis/table?mimNumber=617604,251230

The gene is not associated with any phenotype in G2P.

DONSON is included in gene panels for ID offered by diagnostic laboratories (incl. Radboudumc).

As a result, gene could be considered for inclusion in the ID panel probably as amber (or green) following further review and/or if the phenotype is thought to be relevant.

[Consider also inclusion in other relevant panels apart from microcephaly, eg. limb disorders etc.]
Sources: Literature, Radboud University Medical Center, Nijmegen
Created: 18 Dec 2018, 1:11 p.m.

Mode of inheritance
BIALLELIC, autosomal or pseudoautosomal

Phenotypes
Microcephaly, short stature, and limb abnormalities (MIM 617604); Microcephaly-micromelia syndrome (MIM 251230)

Publications

Variants in this GENE are reported as part of current diagnostic practice

Created: 18 Dec 2018, 1:11 p.m.

Panel version: 2.587

Details

Mode of Inheritance
BIALLELIC, autosomal or pseudoautosomal
Sources
  • Expert Review Amber
  • Expert Review
  • Expert Review
Phenotypes
  • Microcephaly, short stature, and limb abnormalities (MIM 617604)
  • Microcephaly, short stature, and limb abnormalities 617604
  • Microcephaly-micromelia syndrome (MIM 251230)
  • Microcephaly-micromelia syndrome 251230
Tags
watchlist
OMIM
611428
Clinvar variants
Variants in DONSON
Penetrance
unknown
Publications
Panels with this gene

History Filter Activity

25 Jul 2019, Gel status: 2

Added Tag

Catherine Snow (Genomics England)

Tag watchlist tag was added to gene: DONSON.

25 Jul 2019, Gel status: 2

Added New Source, Added New Source, Set Phenotypes, Status Update

Catherine Snow (Genomics England)

Source Expert Review was added to DONSON. Source Expert Review Amber was added to DONSON. Added phenotypes Microcephaly, short stature, and limb abnormalities 617604; Microcephaly-micromelia syndrome 251230 for gene: DONSON Rating Changed from No List (delete) to Amber List (moderate evidence)

18 Dec 2018, Gel status: 0

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

Konstantinos Varvagiannis (Other)

gene: DONSON was added gene: DONSON was added to Intellectual disability. Sources: Literature,Radboud University Medical Center, Nijmegen Mode of inheritance for gene: DONSON was set to BIALLELIC, autosomal or pseudoautosomal Publications for gene: DONSON were set to 28630177; 28191891 Phenotypes for gene: DONSON were set to Microcephaly, short stature, and limb abnormalities (MIM 617604); Microcephaly-micromelia syndrome (MIM 251230) Penetrance for gene: DONSON were set to unknown Review for gene: DONSON was set to AMBER gene: DONSON was marked as current diagnostic