Limb disorders
Gene: GREM1
Not associated with a disease in OMIM and not currently Green on a v1 panel in PanelApp. Associated with HEREDITARY MIXED POLYPOSIS in Gene2Phenotype. In PMID: 20610440 large deletions in a patient with limb disorders, a 1.7 Mb duplication encompassing both the GREM1 and FMN1 genes was detected in a patient with isolated Cenani-Lenz-like oligosyndactyly of the hands, resembling the transgenic chick wings in which Grem1 was over-expressed. GREM1 is involved in limb development (see publications), but there does not seem to be enough evidence at this time that variants in this gene alone can result in limb disorders in patients.Created: 7 Nov 2018, 1:26 p.m.
Mode of inheritance
MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown
Publications
Genomics England clinical team notes - Agree with red rating. No evidence of sequence changes in human limb disease.Created: 9 Sep 2018, 6:16 p.m.
Animal models (chick, mouse) show limb defects (eg PMID: 15198975).
PMID: 20610440 - single patient with homozygous deletion of GREM1 (as well as neighbouring FMN1 - OMIM 136535, which has a mouse model with limb defect) had isolated oligosyndactyly of both hands.
No further publications since 2010.
No small sequence variations described either in publications (search term GREM1 limb, human) or in whole DDD cohort.Created: 24 Apr 2018, 11:15 a.m.
Mode of inheritance
Unknown
Publications
One paper (20610440) to suggest that loss of function variants in this gene are linked to limb abnormalities (among other phenotypes, such as hearing loss and renal function impact). Animal models suggests role in skeletal dysplasia.Created: 5 Apr 2018, 12:41 p.m.
Comment when marking as ready: No direct evidence for involvement in human disease, animal models and in vitro studies suggest a role in skeletal dysplasiaCreated: 12 Jul 2016, 8:02 a.m.
Comment on list classification: No variants reportedCreated: 12 Jul 2016, 8 a.m.
Tier 1Created: 17 Jun 2016, 8:04 a.m.
Mode of inheritance
Unknown
Phenotypes
Cenani Lenz syndactyly 212780
Variants in this GENE are reported as part of current diagnostic practice
Ana Beleza: Tier 1
Gene: grem1 has been classified as Red List (Low Evidence).
Tag watchlist tag was added to gene: GREM1.
Source Expert Review Red was added to GREM1. Mode of inheritance for gene GREM1 was changed from Unknown to MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown Publications for gene GREM1 were changed from 20610440 to 26527308; 22888807; 16908629; 15201225; 20610440; 22965740
Source London South East RGC GSTT was removed from GREM1. Panel: Limb disorders Source Viapath was removed from GREM1. Panel: Limb disorders Literature was added to GREM1. Panel: Limb disorders Model of inheritance for gene GREM1 was set to Unknown Publications for gene GREM1 was set to ['20610440'] structural-variant was added to GREM1. Panel: Limb disorders
London South East RGC GSTT was added to GREM1. Panel: Limb disorders
GREM1 was added to Limb disorders panel. Sources: Viapath
GREM1 was created by Ellen McDonagh