Skeletal dysplasia

Gene: SETD5

Green List (high evidence)

The rating of this gene has been updated to green and the mode of inheritance updated to 'MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted' following NHS Genomic Medicine Service approval.

Created: 4 May 2024, 3:54 p.m. | Last Modified: 4 May 2024, 4:34 p.m.

Panel Version: 5.3

Comment on list classification: As reviewed by Tracy Lester, the observed intellectual developmental disorder phenotype includes skeletal abnormalities ( at least 9 cases) and these might appear before ID. Hence, this gene can be promoted to green rating in the next GMS review.

Created: 8 Aug 2023, 7:37 p.m. | Last Modified: 8 Aug 2023, 7:37 p.m.

Panel Version: 4.14

PMID:24680889 - Of seven patients with SETD5 loss-of-function variants, four had scoliosis or kyphosis, and two had leg-length discrepancy.

PMID:28881385 - Of 14 cases reported with SETD5 variants in this publication, four had scoliosis, kyphosis, lordosis.

Created: 8 Aug 2023, 7:31 p.m. | Last Modified: 8 Aug 2023, 7:31 p.m.

Panel Version: 4.10

Mode of inheritance
MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted

Phenotypes
Intellectual developmental disorder, autosomal dominant 23, OMIM:615761; skeletal dysplasia, MONDO:0018230

Publications

• 24680889
• 28881385

Green List (high evidence)

This gene is associated with an autosomal dominant neurodevelopmental disorder characterised by developmental delay, intellectual disability, and variable dysmorphic and skeletal abnormalities. Expressivity is variable and non-penetrance has been reported. As the skeletal features might appear before the ID/DD I think this gene should be added to the SD panel. We recently found a pathogenic fs in this gene in a child with short stature, short long bones and facial dysmorphism but without mention of DD/ID; however case was only 10m old at referral.
Sources: NHS GMS

Created: 9 Jul 2023, 10:11 a.m.

Mode of inheritance
MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted

Phenotypes
Skeletal dysplasia; intellectual disability; developmental delay; facial dysmorphism

Publications

• 28881385