Skeletal ciliopathies
Gene: LBRComment on mode of inheritance: Appears to be Biallelic in Greenberg dysplasia and in Pelger-Huet anomaly with skeletal anomalies. (Pelger-Huet anomaly without skeletal involvement can be monoallelic)Created: 15 Aug 2019, 1:03 p.m. | Last Modified: 15 Aug 2019, 1:03 p.m.
Panel Version: 0.13
Comment on list classification: Updating from red to green. On the Skeletal ciliopathies panel (rather than the Multisystem ciliopathies panel), it was felt that it could be promoted to green even though the phenotype is not multisystem. It is highly likely to be relevant in childhood.Created: 18 Jul 2019, 2:46 p.m. | Last Modified: 18 Jul 2019, 2:46 p.m.
Panel Version: 0.7
The 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 -
PMID: 21327084 - Clayton et al. (2010) - 3 unrelated fetuses with Greenberg dysplasia. They 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.
PMID: 12618959 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. | Last Modified: 18 Jul 2019, 2:51 p.m.
Panel Version: 0.8
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.
Mode of inheritance for gene: LBR was changed from BIALLELIC, autosomal or pseudoautosomal to BIALLELIC, autosomal or pseudoautosomal
Phenotypes for gene: LBR were changed from Skeletal Ciliopathies to Skeletal Ciliopathies; Greenberg skeletal dysplasia, 215140
Publications for gene: LBR were set to
Gene: lbr has been classified as Green List (High Evidence).
gene: LBR was added gene: LBR was added to Skeletal ciliopathies. Sources: UKGTN,Expert list,Expert Review Red Mode of inheritance for gene: LBR was set to BIALLELIC, autosomal or pseudoautosomal Phenotypes for gene: LBR were set to Skeletal Ciliopathies