Skeletal dysplasia

Gene: SOX9

Green List (high evidence)

Campomelic dysplasia and related disorders gp of SD, brachydactylies (without extraskeletal manifestations) gp of SD. Several cases. translocations with breakpts upstream of gene,deletions upstream of gene, LOF in gene; Review on behalf of Tracy Lester

Created: 6 Mar 2019, 11:44 a.m.

Mode of inheritance
MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted

Phenotypes
Acampomelic campomelic dysplasia 114290; Campomelic dysplasia 114290; Campomelic dysplasia with autosomal sex reversal 114290

Mode of pathogenicity
Other - please provide details in the comments

I don't know

ESHG2020 - Poster E-PO1.34 Ledig et al Report a case of two sisters, 46XY, who are homozygous for a variant, c.1518C>G p.(Leu506Val), in SOX9. The sisters had a suspicion of non-syndromic XY DSD (disorder of sexual development) and no signs of skeletal malformations. By luciferase assay the variant reporte dhereshowed no decrease of transactivating function on Col2a1 promotor in contrast to two SOX9 mutations (c.347C>T p.(Ala116Val) and c.358C>T p.(Arg120Cys)) known to be associated with CD. The authors suggest that SOX9 variant c.1518C>G p.(Leu506Val) is a hypomorphic mutation that causes XY DSD without raising any SOX9 related skeletal phenotype.
No publication relating to this work could be found in PubMed at this time.

Created: 12 Jun 2020, 7:27 p.m. | Last Modified: 12 Jun 2020, 7:27 p.m.

Panel Version: 2.9

This gene was part of an initial gene list collated by Tracy Lester, Oxford Medical Genetics Laboratories, Oxford University Hospitals NHS Foundation Trust, February 2019 on behalf of the GMS Musculoskeletal Specialist Group; Gene symbol submitted: SOX9; Initial rating suggestion: green

Created: 6 Mar 2019, 11:37 a.m.

Green List (high evidence)

Listed as associated with Skeletal Dysplasia by Gene Advisor (June 2016), Steve Abbs

Created: 27 Jul 2016, 9:51 a.m.

Comment on list classification: Used diagnostically by Ana Beleza (Guy's and St Thomas' NHS Foundation Trust)

Created: 21 Jun 2016, 1:10 p.m.

Green List (high evidence)

Tier 1

Created: 17 Jun 2016, 8:08 a.m.

Mode of inheritance
MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown

Phenotypes
Acampomelic campomelic dysplasia 114290; Campomelic dysplasia 114290; Campomelic dysplasia with autosomal sex reversal 114290

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