Skeletal dysplasia

Gene: LMBR1

Green List (high evidence)

Limb hypoplasia-reduction defects gp of SD. Acheiropdy - >3 families reported with exonic deletions of the gene in one. Other phenotypes assocated with variants in the SHH regulatory region (ZRS) located within an intron of LMBR1 - >3 cases reported - ZRS variants associated with Limb hypoplasia-reduction defects gp of SD, polydactyly-syndactyly-triphalangism SD gp, polydactyly-syndactyly-triphalangism SD gp. Only exonic deletions of the gene have been reported. Misssense and dups in the ZRS region within intron 5 only. Do you report variants in this gene as part of your current diagnostic practice? YES - ZRS; Review on behalf of Tracy Lester

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

Mode of inheritance
BOTH monoallelic and biallelic, autosomal or pseudoautosomal

Phenotypes
Acheiropody 200500; Hypoplastic or aplastic tibia with polydactyly 188740; Laurin-Sandrow syndrome 135750; Polydactyly, preaxial type II 174500; Syndactyly, type IV 186200; Triphalangeal thumb, type I 174500; Triphalangeal thumb-polysyndactyly syndrome 174500

Publications

• 26749485
• 11090342

Mode of pathogenicity
Other - please provide details in the comments

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

I don't know

Reported microduplications in LMBR1 associated with Laurin-Sandrow syndrome are in the SHH regulatory element (ZRS) that resides in intron 5 of the LMBR1 gene. Duplications are >10kb and therefore the current pipeline should report these as CNVs within a green gene.

Created: 26 Nov 2019, 4:07 p.m. | Last Modified: 26 Nov 2019, 4:07 p.m.

Panel Version: 1.244

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: LMBR1; Initial rating suggestion: green for ZRS regulatory region and exonic deletions

Created: 6 Mar 2019, 11:36 a.m.

Comment when marking as ready: Numerous variants reported in these phenotypes

Created: 12 Jul 2016, 9:47 a.m.

Green List (high evidence)

Tier 2

Created: 17 Jun 2016, 8:05 a.m.

Mode of inheritance
BOTH monoallelic and biallelic, autosomal or pseudoautosomal

Phenotypes
Acheiropody 200500; Hypoplastic or aplastic tibia with polydactyly 188740; Laurin-Sandrow syndrome 135750; Polydactyly, preaxial type II 174500; Syndactyly, type IV 186200; Triphalangeal thumb, type I 174500; Triphalangeal thumb-polysyndactyly syndrome 174500

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