Rare multisystem ciliopathy disorders
Gene: LBRThe Genomics England rare disease clinical team feedback is that the phenotype described to date (apart from polydactyly) does not strongly suggest a multi-system ciliopathy. If new evidence emerges of multi-system involvement in the ciliopathy spectrum then the rating can be reviewed.Created: 27 Jun 2019, 10:51 a.m. | Last Modified: 27 Jun 2019, 10:51 a.m.
Panel Version: 1.115
Consulting with the Genomics England clinical team as to the appropriate rating for this gene on this panel.Created: 19 Jun 2019, 2:48 p.m.
Associated with Greenberg skeletal dysplasia 215140 as well as several other phenotypes in OMIM. Also known as hydrops-ectopic calcification-moth-eaten (HEM) skeletal dysplasia. Associated with HYDROPS-ECTOPIC CALCIFICATION-MOTH-EATEN SKELETAL DYSPLASIA in Gene2Phenotype (confirmed).
From OMIM -
3 unrelated fetuses with Greenberg dysplasia, Clayton et al. (2010) identified homozygous or compound heterozygous mutations in the LBR gene. Functional assays suggests Greenberg dysplasia results from defects in the sterol reductase activity of LBR, not from the structural function of LBR as part of the nuclear membrane.
Waterham et al. (2003) found elevated levels of cholesta-8,14-dien-3-beta-ol in cultured skin fibroblasts of an 18-week-old fetus with HEM skeletal dysplasia, compatible with a deficiency of the cholesterol biosynthetic enzyme 3-beta-hydroxysterol delta(14)-reductase and identified a mutation in the LBR gene that resulted in a truncated protein.
PMID: 29068549 - Zhang et al 2018 - report a case of a neonate with a non-lethal form of asphyxiating thoracic dystrophy (ATD) and compound heterozygosity for missense mutations LBR .Created: 19 Jun 2019, 2:47 p.m.
Agreed, but may be time to start thinking more broadly about the utility of PanelApp/transition to clinical testing?Created: 7 Aug 2018, 4:13 a.m.
Mode of inheritance
BIALLELIC, autosomal or pseudoautosomal
Phenotypes
Greenberg skeletal dysplasia MIM#215140
Variants in this GENE are reported as part of current diagnostic practice
Comment when marking as ready: Unlikely to fulfil the panel entry criteria -prenatally lethal skeletal dysplasiaCreated: 25 Jan 2017, 1:21 p.m.
Promoted to version 1 by Alice Gardham on 26th January 2017
This gene has been classified as Red List (Low Evidence).
LBR was added to Rare multisystem ciliopathy disorderspanel. Sources: UKGTN
Phenotypes for gene LBR were set to Skeletal Ciliopathies
LBR was added to Rare multisystem ciliopathy disorderspanel. Sources: Expert list
LBR was created by ellenmcdonagh