Limb disorders

Gene: GREM1

Red List (low evidence)

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

• 20610440
• 26527308
• 22888807
• 22965740
• 15201225
• 16908629

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.

Red List (low evidence)

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

• PMID: 20610440

Red List (low evidence)

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 dysplasia

Created: 12 Jul 2016, 8:02 a.m.

Comment on list classification: No variants reported

Created: 12 Jul 2016, 8 a.m.

Green List (high evidence)

Tier 1

Created: 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