Intellectual disability update Jan 2018

Gene: GJB1

Amber List (moderate evidence)

GJB1 (gap junction protein beta 1)
EnsemblGeneIds (GRCh38): ENSG00000169562
EnsemblGeneIds (GRCh37): ENSG00000169562
OMIM: 304040, Gene2Phenotype
GJB1 is in 7 panels

2 reviews

Helen Brittain (Genomics England Curator)

Comment when marking as ready: Typical phenotype is not a good fit for this panel. I note the small number of reports of patients with more prominent ID than neuropathic presentation, however on the current evidence I would expect the greatest diagnostic yield to be from the presence of this gene on the CMT panel.
Created: 6 Mar 2018, 5:05 p.m.

Sarah Leigh (Genomics England Curator)

Associated with phenotype in OMIM, not in G2P. Numerous variants reported in Charcot-Marie-Tooth neuropathy, X-linked dominant, 1 302800, however, intellectual disability or cognitive impairment has only been reported in a minority of cases. PMID 26385972 reports cognitive impairment in 4 adult cases and PMID 23279342 reports a proband and her sister with severe neuropathy and subclinical cognitive impairment, while the proband's brother showed severe cognitive impairment and mild neuropathy.
Reported as a gene linked to isolated ID and ID associated disorders Vissers 2016 (PMID 26503795)
Created: 5 Mar 2018, 12:34 p.m.

Details

Mode of Inheritance
X-LINKED: hemizygous mutation in males, monoallelic mutations in females may cause disease (may be less severe, later onset than males)
Sources
  • Expert Review Amber
  • Radboud University Medical Center, Nijmegen
Phenotypes
  • Charcot-Marie-Tooth neuropathy, X-linked dominant, 1 302800
OMIM
304040
Clinvar variants
Variants in GJB1
Penetrance
None
Publications
Panels with this gene

History Filter Activity

6 Mar 2018, Gel status: 2

Gene classified by Genomics England curator

Helen Brittain (Genomics England Curator)

This gene has been classified as Amber List (Moderate Evidence).

5 Mar 2018, Gel status: 2

Gene classified by Genomics England curator

Sarah Leigh (Genomics England Curator)

This gene has been classified as Amber List (Moderate Evidence).

5 Mar 2018, Gel status: 1

Set publications

Sarah Leigh (Genomics England Curator)

Publications for GJB1 were set to 26503795; 23279342; 26385972

5 Mar 2018, Gel status: 1

Set mode of inheritance

Sarah Leigh (Genomics England Curator)

Mode of inheritance for GJB1 was changed from to X-LINKED: hemizygous mutation in males, monoallelic mutations in females may cause disease (may be less severe, later onset than males)

5 Mar 2018, Gel status: 1

Set Phenotypes

Sarah Leigh (Genomics England Curator)

Phenotypes for GJB1 were set to Charcot-Marie-Tooth neuropathy, X-linked dominant, 1 302800

18 Dec 2017, Gel status: 1

Added New Source

Ellen McDonagh (Genomics England Curator)

GJB1 was added to Intellectual disability update Jan 2018 panel. Sources: Radboud University Medical Center, Nijmegen,Expert Review Red

18 Dec 2017, Gel status: 1

Created

Ellen McDonagh (Genomics England Curator)

GJB1 was created by Ellen McDonagh