Fetal anomalies
Gene: GJB2This gene was included due to the possibility that digital constrictions might present prenatally. However, PMID:24346921 reports that the phenotype usually manifests in infants and worsens in adulthood. Since it is unlikely that the features would be severe enough to be detected on fetal ultrasound, and given the high carrier frequency for variants associated with AR sensorineural deafness, it may be more appropriate to exclude this gene from the fetal anomalies panel.Created: 9 Sep 2019, 1:38 a.m. | Last Modified: 9 Sep 2019, 1:38 a.m.
Panel Version: 0.339
Publications
Note that GJB2 is no longer present on the DD panel of Gene2Phenotype. All GJB2 phenotypes (May 2020) are associated with the Gene2Phenotype skin panel. Red rating is still appropriate for this Fetal panel.Created: 12 May 2020, 7:13 p.m. | Last Modified: 12 May 2020, 7:13 p.m.
Panel Version: 1.59
Comment on list classification: Demoted GJB2 from Green to Red as requested by Anna de Burca. See Anna's review (9 September 2019)- the digit phenotype is unlikely to be detected on fetal ultrasound.Created: 9 Sep 2019, 3:49 p.m. | Last Modified: 9 Sep 2019, 3:49 p.m.
Panel Version: 0.340
Comment on mode of inheritance: In original PAGE file, inheritance was listed as biallelic for 'DEAFNESS AUTOSOMAL RECESSIVE TYPE 1A' and monoallelic for 'PALMOPLANTAR KERATODERMA WITH DEAFNESS', 'ICHTHYOSIS HYSTRIX-LIKE WITH DEAFNESS SYNDROME', 'VOHWINKEL SYNDROME' and 'BART-PUMPHREY SYNDROME'. Changed MOI to 'monoallelic' only following clinical review because the deafness phenotype alone is not detectable pre-natally.Created: 24 Mar 2019, 8:26 p.m.
This gene and phenotype were reviewed during meetings at Great Ormond Street hospital in March 2019. Clinical review and curation was performed by Lyn Chitty, Anna de Burca, Rhiannon Mellis, Richard Scott, Ellen McDonagh and Rebecca Foulger. Outcome of review: Confirmed that phenotype is fetally-relevant: keep on the Fetal anomalies panel as Green. Additional notes from clinical review: Include on panel on basis of possible congenital digit constrictions and no harm done. Change MOI to monoallelic only: Recessive inheritance is attributed to the deafness phenotype, which would not be detected prenatally. Action taken: Changed mode of inheritance from 'both biallelic and monoallelic' to 'monoallelic' only.Created: 24 Mar 2019, 4:30 p.m.
DDG2P rating in original PAGE list: Confirmed for DEAFNESS AUTOSOMAL RECESSIVE TYPE 1A, Confirmed for PALMOPLANTAR KERATODERMA WITH DEAFNESS, Confirmed for ICHTHYOSIS HYSTRIX-LIKE WITH DEAFNESS SYNDROME, Confirmed for VOHWINKEL SYNDROME and Confirmed for BART-PUMPHREY SYNDROME.Created: 11 Dec 2018, 9:05 a.m.
In the original PAGE file, MOP listed as LOF for DEAFNESS AUTOSOMAL RECESSIVE TYPE 1A, and listed as All missense/in frame for PALMOPLANTAR KERATODERMA WITH DEAFNESS, ICHTHYOSIS HYSTRIX-LIKE WITH DEAFNESS SYNDROME, VOHWINKEL SYNDROME and BART-PUMPHREY SYNDROME.Created: 8 Nov 2018, 4:45 p.m.
Mode of inheritance
MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown
Publications for gene: GJB2 were set to 23035047
Gene: gjb2 has been classified as Red List (Low Evidence).
Publications for gene: GJB2 were set to
Mode of inheritance for gene: GJB2 was changed from MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown to MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown
Mode of inheritance for gene GJB2 was changed from BOTH monoallelic and biallelic, autosomal or pseudoautosomal to MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown
Added phenotypes BART-PUMPHREY SYNDROME for gene: GJB2
Added phenotypes VOHWINKEL SYNDROME for gene: GJB2
Added phenotypes ICHTHYOSIS HYSTRIX-LIKE WITH DEAFNESS SYNDROME for gene: GJB2
Added phenotypes PALMOPLANTAR KERATODERMA WITH DEAFNESS for gene: GJB2
gene: GJB2 was added gene: GJB2 was added to Fetal anomalies. Sources: Expert Review Green,PAGE DD-Gene2Phenotype Mode of inheritance for gene: GJB2 was set to BOTH monoallelic and biallelic, autosomal or pseudoautosomal Phenotypes for gene: GJB2 were set to DEAFNESS AUTOSOMAL RECESSIVE TYPE 1A