Skeletal dysplasia
Gene: RBPJ
Brachydactylies (with extraskeletal manifestations) gp of SD - only 2 unrelated families reported?; Review on behalf of Tracy LesterCreated: 6 Mar 2019, 11:44 a.m.
Mode of inheritance
MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Phenotypes
Adams-Oliver syndrome 3, 614814
Publications
PMID: 29924900 - Meester et al 2018 - analyzed a cohort comprised of 194 distinct Adams–Oliver syndrome/scalp aplasia cutis congenita (ACC)/transverse terminal limb defects (TTLD) familial or sporadic cases. Most analysed using targeted next‐generation resequencing in 6 established AOS genes including RBPJ. They report 4 families in which likely heterozygous pathogenic/pathogenic variants were found in RBPJ. All were inherited in an autosomal dominant manner. 3 are novel mutations, 1 has been reported previously in another family. All 4 families showed transverse terminal limb defects, while 3 out of 4 also were positive for scalp aplasia cutis congenita. One family also displayed microcephaly and hip dislocationCreated: 16 Jul 2019, 3:01 p.m. | Last Modified: 16 Jul 2019, 3:03 p.m.
Panel Version: 1.167
PMID: 22883147 - Hassed et al. 2012 - identified mutations in RBPJ through exome sequencing in two independent kindreds with autosomal dominant AOS.
PMID: 28160419 - Hassad et al 2017 - don't think they report any new families.Created: 7 May 2019, 9:57 p.m. | Last Modified: 16 Jul 2019, 3:03 p.m.
Panel Version: 1.167
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: RBPJ; Initial rating suggestion: amberCreated: 6 Mar 2019, 11:36 a.m.
The Adams–Oliver syndrome (AOS) is defined as aplasia cutis congenita (ACC) with transverse terminal limb defects (TTLD). Six causative genes have been identified: ARHGAP31, DOCK6, EOGT, RBPJ, NOTCH1, and DLL4. In PMID: 28160419 (2017) 385 previously described individuals (139 non-familial and 246 familial probands and family members) and clinical data on 13 previously unreported individuals with AOS was assessed and it was found that in addition to ACC and TTLD, the most commonly associated anomalies, there were other phenotypes specific to the causative gene.Created: 2 Nov 2017, 12:10 p.m.
Comment on list classification: Changed from Red to Green based on expert review and current literature updates that refine the diagnostic phenotype.Created: 2 Nov 2017, 12:04 p.m.
Comment on publications: added 2017 publication (PMID: 28160419) to support more cases where RBPJ is shown to cause Adams-Oliver syndrome 3 in 6 cases.Created: 2 Nov 2017, 12:02 p.m.
Comment when marking as ready: Associated with phenotype in OMIM and G2P. At least two variants reportedCreated: 29 Jul 2016, 1:59 p.m.
Tier 2Created: 17 Jun 2016, 8:07 a.m.
Mode of inheritance
MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Phenotypes
Adams-Oliver syndrome 3 614814
Variants in this GENE are reported as part of current diagnostic practice
Publications for gene: RBPJ were set to 28160419; 22883147
Added phenotypes Adams-Oliver syndrome 3, 614814 for gene: RBPJ Publications for gene RBPJ were changed from 22883147; 28160419 to 28160419; 22883147
Source NHS GMS was added to RBPJ. Rating Changed from Green List (high evidence) to Green List (high evidence)
Publications for RBPJ were set to 22883147;28160419
Phenotypes for RBPJ were set to Adams-Oliver syndrome 3, 614814
This gene has been classified as Green List (High Evidence).
Publications for RBPJ were set to 22883147
This gene has been classified as Amber List (Moderate Evidence).
Promoted to version 1 9th August 2016
This gene has been classified as Red List (Low Evidence).
Phenotypes for RBPJ were set to Adams-Oliver syndrome 3 614814
Mode of inheritance for RBPJ was changed to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
RBPJ was added to Unexplained skeletal dysplasiapanel. Sources: Expert list,Radboud University Medical Center, Nijmegen
RBPJ was added to Unexplained skeletal dysplasiapanel. Sources:
RBPJ was created by sleigh