Limb disorders
Gene: SHH
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
Variants and duplications in the regulatory ZRS region within intron LMBR1 which affect the expression of SHH have been reviewed in gene LMBR1 on this panel.Created: 26 Nov 2019, 3 p.m. | Last Modified: 26 Nov 2019, 3 p.m.
Panel Version: 1.127
Genomic England clinical team notes - Agree with red rating. No evidence of sequence changes in SHH itself causing limb phenotype in humansCreated: 9 Sep 2018, 7:53 p.m.
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 panelCreated: 24 Apr 2018, 12:24 p.m.
Mode of inheritance
Unknown
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.
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 1Created: 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 147250Created: 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.
Tier 2Created: 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
Ana Beleza: Tier 2
Gene: shh has been classified as Red List (Low Evidence).
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
Victorian Clinical Genetics Services was added to SHH. Panel: Limb disorders Phenotypes for gene SHH were set to preaxial polydactyly, holoprosencephaly, Polydactyly
Publications for SHH were set to 12032320; 12837695; 25782671
This gene has been classified as Red List (Low Evidence).
SHH was added to Limb disorders panel. Sources: Literature
SHH was created by Dimitris Polychronopoulos