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Mendeliome v1.4586 POU3F4 upstream regulatory region Sarah Milton Region: POU3F4 upstream regulatory region was added
Region: POU3F4 upstream regulatory region was added to Mendeliome. Sources: Literature
Mode of inheritance for Region: POU3F4 upstream regulatory region was set to X-LINKED: hemizygous mutation in males, biallelic mutations in females
Publications for Region: POU3F4 upstream regulatory region were set to PMID: 41170199, 35189936, 33860785
Phenotypes for Region: POU3F4 upstream regulatory region were set to Deafness, X-linked 2 MIM#304400
Review for Region: POU3F4 upstream regulatory region was set to AMBER
Added comment: POU3F4 encodes POU domain, class III, transcriptional factor 4, a transcription factor with functional targets not fully elucidated but known to affect expression of GJB6, EPHA4 and EFNB2 in development.

17 patients reported across a number of publications with deletions sized between 8kb to 1.74mb upstream of POU3F4 presented with X linked deafness.

Yang et al PMID: 41170199 reported 4 male individuals from one pedigree with deafness segregating with the upstream deletion.
qPCR demonstrated reduced mRNA expression of POU3F4 in two affected males with the deletion with normal levels in their unaffected father.

It is proposed this deletion is removing an upstream enhancer element however functional studies have not been performed to demonstrate this as of yet.

The coordinates used in this entry are the largest reported to cause the phenotype most deletions reported in affected individuals were smaller.
Sources: Literature
Mendeliome v1.2224 CRYL1 Andrew Fennell changed review comment from: About 1% of individuals with GJB2-AR NSHL are compound heterozygotes for one GJB2 pathogenic variant and one of several different deletions that include sequences upstream of GJB2 (comprising either GJB6 and portions of CRYL1 or just portions of CRYL1) that delete cis-regulatory regions of GJB2, thereby abolishing GJB2 expression. Occasionally, the deletion also includes GJB2.; to: About 1% of individuals with GJB2-AR NSHL are compound heterozygotes for one GJB2 pathogenic variant and one of several different deletions that include sequences upstream of GJB2 (comprising either GJB6 and portions of CRYL1 or just portions of CRYL1) that delete cis-regulatory regions of GJB2, thereby abolishing GJB2 expression. Occasionally, the deletion also includes GJB2.
See also PMID: 20301449 GeneReviews
Mendeliome v0.14637 GJB6 Zornitza Stark Marked gene: GJB6 as ready
Mendeliome v0.14637 GJB6 Zornitza Stark Gene: gjb6 has been classified as Green List (High Evidence).
Mendeliome v0.14637 GJB6 Zornitza Stark Phenotypes for gene: GJB6 were changed from to Deafness, autosomal dominant 3B, MIM# 612643; Deafness, autosomal recessive 1B, MIM# 612645; Ectodermal dysplasia 2, Clouston type, MIM# 129500
Mendeliome v0.14636 GJB6 Zornitza Stark Publications for gene: GJB6 were set to
Mendeliome v0.14635 GJB6 Zornitza Stark Mode of inheritance for gene: GJB6 was changed from Unknown to BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Mendeliome v0.14634 GJB6 Zornitza Stark Tag SV/CNV tag was added to gene: GJB6.
Mendeliome v0.14634 GJB6 Zornitza Stark reviewed gene: GJB6: Rating: GREEN; Mode of pathogenicity: None; Publications: 11017065, 23219093, 11874494, 18717672, 27137747, 25808784, 19416251, 26620415, 17227867; Phenotypes: Deafness, autosomal dominant 3B, MIM# 612643, Deafness, autosomal recessive 1B, MIM# 612645, Ectodermal dysplasia 2, Clouston type, MIM# 129500; Mode of inheritance: BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Mendeliome v0.0 GJB6 Zornitza Stark gene: GJB6 was added
gene: GJB6 was added to Mendeliome_VCGS. Sources: Expert Review Green,Victorian Clinical Genetics Services
Mode of inheritance for gene: GJB6 was set to Unknown