| Date | Panel | Item | Activity | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Mendeliome v2.311 | PPL |
chirag patel gene: PPL was added gene: PPL was added to Mendeliome. Sources: Literature Mode of inheritance for gene: PPL was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted Publications for gene: PPL were set to 34815391 Phenotypes for gene: PPL were set to Eosinophilic esophagitis, MONDO:0005361 Review for gene: PPL was set to GREEN Added comment: PMID 34815391 reports 17 affected individuals from 7 families with eosinophilic oesophagitis and 6 different heterozygous missense PPL variants. Most variants are rare but 2 are seen in 140 hets (p.Val1377Glu) and 159 hets (p.Glu632Lys) in gnomAD v4. The variants segregated with affected siblings/relatives in 6/7 families, and parental testing was only done in 2/7 families with reduced penetrance noted in those families. One large family also had a DSP (desmoplakin variant segregating with disease). Periplakin (PPL) is a member of the plakin protein family that localize to desmosomes and is highly expressed in the esophagus. PPL knockout EPC2 cells (human esophageal cell lines) demonstrated acantholysis and significantly decreased barrier function. EPC2 cells transduced with PPL variants showed impaired epithelial barrier integrity and reduced barrier function. A wound healing assay showed mutant PPL increased wound‑healing speed, reduced active RhoA, and increased susceptibility to CAPN14‑mediated degradation. Sources: Literature |
|||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v2.0 | RHOA | Gene migrated from ENSG00000067560 to ENSG00000067560 (gene set migration) | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v1.3529 | RHOA | Zornitza Stark Phenotypes for gene: RHOA were changed from normal cognition; leukoencephalopathy; micro-ophthalmia; strabismus; linear hypopigmentation; malar hypoplasia; downslanting palpebral fissures; microstomia; dental anomalies; body asymmetry; limb length discrepancy to Ectodermal dysplasia with facial dysmorphism and acral, ocular, and brain anomalies, somatic mosaic, MIM# 618727 | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v1.3528 | RHOA | Zornitza Stark Publications for gene: RHOA were set to 31570889; 31821646 | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v1.3527 | RHOA | Zornitza Stark edited their review of gene: RHOA: Changed phenotypes: Ectodermal dysplasia with facial dysmorphism and acral, ocular, and brain anomalies, somatic mosaic, MIM# 618727 | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v1.3527 | RHOA | Zornitza Stark edited their review of gene: RHOA: Added comment: PMID 40414526: non-mosaic individual reported.; Changed publications: 31821646, 40414526 | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v1.2336 | GNA13 |
Bryony Thompson gene: GNA13 was added gene: GNA13 was added to Mendeliome. Sources: Literature Mode of inheritance for gene: GNA13 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted Publications for gene: GNA13 were set to 39966435 Phenotypes for gene: GNA13 were set to Ito hypomelanosis MONDO:0010302 Mode of pathogenicity for gene: GNA13 was set to Other Review for gene: GNA13 was set to AMBER Added comment: 4 unrelated cases with a recurrent post-zygotic GNA13 variant (NM_006572.4:c.599G>A p.Arg200Lys) with a syndrome including hypomelanosis of Ito associated with developmental anomalies. The variant was identified in one patient via exome sequencing of paired tissue/blood and then targeted GNA13 testing of other cases. In vitro assays demonstrate a gain of function for the variant. Q226L was an artificial variant demonstrating a gain of function similar to R200K. The suggested mechanism of disease is through upregulation of the RHOA/ROCK pathway altering melanocyte function. Sources: Literature |
|||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.11010 | DLC1 |
Bryony Thompson gene: DLC1 was added gene: DLC1 was added to Mendeliome. Sources: Expert list Mode of inheritance for gene: DLC1 was set to BIALLELIC, autosomal or pseudoautosomal Publications for gene: DLC1 were set to 29773874 Phenotypes for gene: DLC1 were set to Nephrotic syndrome MONDO:0005377 Review for gene: DLC1 was set to GREEN Added comment: Biallelic variants in 4 families, and knockdown of DLC1 in cultured podocytes reduces migration rate and treatment with dexamethasone abolishes RhoA activation. Sources: Expert list |
|||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.2577 | RHOA | Zornitza Stark Phenotypes for gene: RHOA were changed from normal cognition; leukoencephalopathy; micro-ophthalmia; strabismus; linear hypopigmentation; malar hypoplasia; downslanting palpebral fissures; microstomia to normal cognition; leukoencephalopathy; micro-ophthalmia; strabismus; linear hypopigmentation; malar hypoplasia; downslanting palpebral fissures; microstomia; dental anomalies; body asymmetry; limb length discrepancy | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.2576 | RHOA | Zornitza Stark Publications for gene: RHOA were set to 31570889 | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.2575 | RHOA | Zornitza Stark reviewed gene: RHOA: Rating: GREEN; Mode of pathogenicity: None; Publications: 31821646; Phenotypes: hypopigmented areas of the skin, dental anomalies, body asymmetry, limb length discrepancy, MRI abnormalities; Mode of inheritance: Other | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.701 | RHOA | Zornitza Stark Tag somatic tag was added to gene: RHOA. | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.698 | RHOA | Sue White Marked gene: RHOA as ready | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.698 | RHOA | Sue White Gene: rhoa has been classified as Green List (High Evidence). | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.698 | RHOA | Sue White Classified gene: RHOA as Green List (high evidence) | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.698 | RHOA | Sue White Gene: rhoa has been classified as Green List (High Evidence). | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.697 | RHOA |
Sue White gene: RHOA was added gene: RHOA was added to Mendeliome_VCGS. Sources: Literature Mode of inheritance for gene: RHOA was set to Other Publications for gene: RHOA were set to 31570889 Phenotypes for gene: RHOA were set to normal cognition; leukoencephalopathy; micro-ophthalmia; strabismus; linear hypopigmentation; malar hypoplasia; downslanting palpebral fissures; microstomia Penetrance for gene: RHOA were set to Complete Review for gene: RHOA was set to GREEN gene: RHOA was marked as current diagnostic Added comment: mosaic heterozygous missense variants cause linear hypopigmentation, brain MRI changes with normal cognition, ocular and acral changes Sources: Literature |
|||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||