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Limb disorders

Gene: SHH

Red List (low evidence)

SHH (sonic hedgehog)
EnsemblGeneIds (GRCh38): ENSG00000164690
EnsemblGeneIds (GRCh37): ENSG00000164690
OMIM: 600725, Gene2Phenotype
SHH is in 18 panels

7 reviews

Louise Daugherty (Genomics England Curator)

Red List (low evidence)

Agree with Red rating, need more evidence to support gene-disease association in humans for the Preaxial polydactyly phenotype. Publications supporting a relevant phenotypes have only been demonstrated in mouse models (PMID:12032320, 12837695)
Created: 7 Nov 2018, 1:26 p.m.

Mode of inheritance
MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted

Phenotypes
Preaxial polydactyly; Polydactyly

Publications

Eleanor Williams (Genomics England Curator)

Genomic England clinical team notes - Agree with red rating. No evidence of sequence changes in SHH itself causing limb phenotype in humans
Created: 9 Sep 2018, 7:53 p.m.

Rachel Jones (GSTT)

Red List (low evidence)

No publications of sequence changes in SHH itself associated with limb phenotype.

https://www.ncbi.nlm.nih.gov/pubmed/25782671 concerns 2kb deletion of a 240kb upstream regulatory region of SHH which represses transriptional activity of SHH promoter.

LMBR1 aka ZRS long range enhancer is already on panel
Created: 24 Apr 2018, 12:24 p.m.

Mode of inheritance
Unknown

Ellen McDonagh (Genomics England Curator)

Comment on list classification: Added gene to panel, for review. This gene has a role in limb development.
Created: 14 Dec 2017, 4:49 p.m.

Dimitris Polychronopoulos (Genomics England)

I don't know

Mode of inheritance
Unknown

Phenotypes
preaxial polydactyly; holoprosencephaly

Publications

Sarah Leigh (Genomics England Curator)

The only variant associated with preaxial polydactyly-hypertrichosis is 2 kb deletion located ~240 kb upstream from the SHH promoter.
Created: 5 Apr 2018, 12:29 p.m.
Comment when marking as ready: Not associated with relevant phenotype on G2P or OMIM. Single variant reported in Preaxial polydactyly type 1
Created: 12 Jul 2016, 1:02 p.m.
Comment on phenotypes: Variants in SHH associated with the following phenotypes, which are not relevant for Skeletal dysplasia: Holoprosencephaly 3 142945; Microphthalmia with coloboma 5 611638; Schizencephaly 269160; Single median maxillary central incisor 147250
Created: 12 Jul 2016, 1:01 p.m.
Comment on publications: Report of 2 kb deletion located ~240 kb upstream from the SHH promoter.
Created: 12 Jul 2016, 12:58 p.m.

Ana Beleza (Bristol Regional Genetics Service)

Green List (high evidence)

Tier 2
Created: 17 Jun 2016, 8:08 a.m.

Mode of inheritance
MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted

Phenotypes
Petit F, et al. The disruption of a novel limb cis-regulatory element of SHH is associated with autosomal dominant preaxial polydactyly-hypertrichosis. Eur J Hum Genet. 2016 Jan 24(1), 37-43; Holoprosencephaly 3 142945; Microphthalmia with coloboma 5 611638; Schizencephaly 269160; Single median maxillary central incisor 147250

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

Details

History Filter Activity

11 Dec 2018, Gel status: 1

Panel promoted to version 1.0

Eleanor Williams (Genomics England Curator)

Ana Beleza: Tier 2

7 Nov 2018, Gel status: 1

Entity classified by Genomics England curator

Eleanor Williams (Genomics England Curator)

Gene: shh has been classified as Red List (Low Evidence).

7 Nov 2018, Gel status: 1

Set mode of inheritance, Set Phenotypes, Set publications

Eleanor Williams (Genomics England Curator)

Mode of inheritance for gene SHH was changed from Unknown to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted Added phenotypes Preaxial polydactyly; Polydactyly for gene: SHH Publications for gene SHH were changed from 12032320; 12837695; 25782671 to 25782671; 12837695; 12032320

13 Aug 2018, Gel status: 1

Added New Source, Set penetrance

Ellen McDonagh (Genomics England Curator)

Victorian Clinical Genetics Services was added to SHH. Panel: Limb disorders Phenotypes for gene SHH were set to preaxial polydactyly, holoprosencephaly, Polydactyly

5 Apr 2018, Gel status: 1

Set publications

Sarah Leigh (Genomics England Curator)

Publications for SHH were set to 12032320; 12837695; 25782671

14 Dec 2017, Gel status: 1

Gene classified by Genomics England curator

Ellen McDonagh (Genomics England Curator)

This gene has been classified as Red List (Low Evidence).

13 Dec 2017, Gel status: 0

Added New Source

Dimitris Polychronopoulos (Genomics England)

SHH was added to Limb disorders panel. Sources: Literature

13 Dec 2017, Gel status: 0

Created

Dimitris Polychronopoulos (Genomics England)

SHH was created by Dimitris Polychronopoulos