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Fetal anomalies v1.558 DLX5 downstream regulatory region Sarah Milton GRCh38 position for DLX5 downstream regulatory region was changed from 95772554-96098424 to 96075000-96100000.
Fetal anomalies v1.557 DLX5 downstream regulatory region Sarah Milton changed review comment from: DLX5 encodes a transcription factor essential for epidermal morphogenesis and limb development. Expression is known to be regulated by p63 (encoded for by TP63).

Over 20 families have been reported with deletions or translocations involving a region downstream from DLX5 with split-hand foot malformation with incomplete penetrance.
Deletions are highly variable in size ranging from 17kb to megabase in size.

The region deleted is located within the protein coding gene DYNC1I1. However haploinsufficiency of this gene is not thought to be the mechanism of disease . It has been demonstrated enhancer elements that regulate expression of DLX5 are located within exons 14-17 of DYNC1I1 with individuals with balanced translocations disrupting the region also having a similar phenotype.

Note: coordinates used for this entry are that of the refseq for DYNC1I1, much larger or smaller deletions or disruption to the region from translocations/inversions may still be causative of disease.
Sources: Literature; to: DLX5 encodes a transcription factor essential for epidermal morphogenesis and limb development. Expression is known to be regulated by p63 (encoded for by TP63).

Over 20 families have been reported with deletions or translocations involving a region downstream from DLX5 with split-hand foot malformation with incomplete penetrance.
Deletions are highly variable in size ranging from 17kb to megabase in size.

The region deleted is located within the protein coding gene DYNC1I1. However haploinsufficiency of this gene is not thought to be the mechanism of disease . It has been demonstrated enhancer elements that regulate expression of DLX5 are located within exons 14-17 of DYNC1I1 with individuals with balanced translocations disrupting the region also having a similar phenotype.

Note: coordinates used for this entry encompass exons 14 to 17 of DYNC1I1, much larger deletions or disruption to the region from translocations/inversions may still be causative of disease
Sources: Literature
Fetal anomalies v1.557 Sarah Milton Copied Region DLX5 downstream regulatory region from panel Mendeliome
Fetal anomalies v1.557 DLX5 downstream regulatory region Sarah Milton Region: DLX5 downstream regulatory region was added
Region: DLX5 downstream regulatory region was added to Fetal anomalies. Sources: Literature
regulatory region tags were added to Region: DLX5 downstream regulatory region.
Mode of inheritance for Region: DLX5 downstream regulatory region was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for Region: DLX5 downstream regulatory region were set to PMID: 26839112; 37916192; 26075025; 24459211
Phenotypes for Region: DLX5 downstream regulatory region were set to Split-hand/foot malformation 1 MIM#183600
Penetrance for Region: DLX5 downstream regulatory region were set to Incomplete
Fetal anomalies v1.547 DLX5 Zornitza Stark Publications for gene: DLX5 were set to 22121204; 24496061; 25196357; 20534536; 12112878
Fetal anomalies v1.546 DLX5 Zornitza Stark reviewed gene: DLX5: Rating: GREEN; Mode of pathogenicity: None; Publications: 41760400; Phenotypes: ; Mode of inheritance: BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Fetal anomalies v0.2366 DYNC1I1 Krithika Murali gene: DYNC1I1 was added
gene: DYNC1I1 was added to Fetal anomalies. Sources: Literature
Mode of inheritance for gene: DYNC1I1 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: DYNC1I1 were set to 22914741; 25231166; 32219838
Phenotypes for gene: DYNC1I1 were set to Split-hand/split-foot malformation (SHFM)
Review for gene: DYNC1I1 was set to GREEN
Added comment: Gene disease association reviewed Sept 2021 - no new publications

At least 6 unrelated families with overlapping deletions that included exons 15 and 17 of DYNC1I1. Exons 15 and 17 have previously been shown to act as tissue-specific enhancers of Dlx5/6 in mouse and zebrafish. No SNVs reported in association with disease.
Sources: Literature
Fetal anomalies v0.2289 DLX5 Zornitza Stark Marked gene: DLX5 as ready
Fetal anomalies v0.2289 DLX5 Zornitza Stark Gene: dlx5 has been classified as Green List (High Evidence).
Fetal anomalies v0.2289 DLX5 Zornitza Stark Phenotypes for gene: DLX5 were changed from ?Split-hand/foot malformation 1 with sensorineural hearing loss, 220600; Split-hand/foot malformation 1, 183600 to Split-hand/foot malformation 1 with sensorineural hearing loss MIM#220600; Split-hand/foot malformation 1 MIM#183600
Fetal anomalies v0.2288 DLX5 Zornitza Stark Publications for gene: DLX5 were set to
Fetal anomalies v0.2287 DLX5 Zornitza Stark Classified gene: DLX5 as Green List (high evidence)
Fetal anomalies v0.2287 DLX5 Zornitza Stark Gene: dlx5 has been classified as Green List (High Evidence).
Fetal anomalies v0.1725 DLX5 Belinda Chong reviewed gene: DLX5: Rating: GREEN; Mode of pathogenicity: None; Publications: 22121204, 24496061, 25196357, 20534536, 12112878; Phenotypes: Split-hand/foot malformation 1 with sensorineural hearing loss MIM#220600, Split-hand/foot malformation 1 MIM#183600; Mode of inheritance: BOTH monoallelic and biallelic, autosomal or pseudoautosomal; Current diagnostic: yes
Fetal anomalies v0.1725 DLX5 Belinda Chong Deleted their review
Fetal anomalies v0.1725 DLX5 Belinda Chong reviewed gene: DLX5: Rating: GREEN; Mode of pathogenicity: None; Publications: 22121204, 24496061, 25196357, 20534536, 12112878; Phenotypes: ; Mode of inheritance: BOTH monoallelic and biallelic, autosomal or pseudoautosomal; Current diagnostic: yes
Fetal anomalies v0.0 DLX5 Zornitza Stark gene: DLX5 was added
gene: DLX5 was added to Fetal anomalies. Sources: Expert Review Amber,Genomics England PanelApp
Mode of inheritance for gene: DLX5 was set to BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Phenotypes for gene: DLX5 were set to ?Split-hand/foot malformation 1 with sensorineural hearing loss, 220600; Split-hand/foot malformation 1, 183600