| Date | Panel | Item | Activity | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Mendeliome v2.106 | TMEM63B |
Eleanor Williams changed review comment from: Heterozygous variants in TMEM63B are associated with Developmental and epileptic encephalopathy 118 (OMIM:621250, accessed 25th Jun 2026) with a gain-of-function mechanism proposed. Variants reported are either missense or an in-frame deletion. The main phenotypic features are severe early-onset developmental and epileptic encephalopathy, intellectual disability, and severe motor and cortical visual impairment associated with progressive neurodegenerative brain changes (PMID: 37421948, doi:10.1016/j.bdcasr.2024.100043). Hearing loss is reported in mouse TMEM63B knockouts PMID: 32375046). PMID: 42259295 Chan et al 2026 report five individuals from four unrelated families with childhood interstitial lung disease and biallelic predicted loss-of-function variants in TMEM63B. Other phenotypic characteristics include moderate/severe developmental delay (5/5), white matter changes, (1/5), mild global atrophy on brain imaging (1/5) and severe short stature (2/5). None of the individuals had epilepsy or hearing loss. Individuals were from Saudi Arabian, Malay, European and Native American ethnicities. 5 different variants were reported including nonsense, frameshift and splice donor variants. In family A a heterozygous ABCA3 missense variant of unknown significance was also inherited from the mother. Biallelic variants in ABCA3 are associated with Surfactant metabolism dysfunction, pulmonary, 3, OMIM:610921. The authors report that while there are 53 TMEM63B pLoF variants in gnomAD v.4.1.0 database none are in the homozygous state. Histopathological examination of lung tissue also showed a pattern consistent with surfactant dysfunction. The authors conclude that biallelic loss of function variants result in a distinct pulmonary-predominant phenotype characterized by hypoxemia, early-onset respiratory failure, histological features of surfactant dysfunction, and chest imaging consistent with chILD.; to: Heterozygous variants in TMEM63B are associated with Developmental and epileptic encephalopathy 118 (OMIM:621250, accessed 25th Jun 2026) with a gain-of-function mechanism proposed. PMID: 42259295 Chan et al 2026 report five individuals from four unrelated families with childhood interstitial lung disease and biallelic predicted loss-of-function variants in TMEM63B. Other phenotypic characteristics include moderate/severe developmental delay (5/5), white matter changes, (1/5), mild global atrophy on brain imaging (1/5) and severe short stature (2/5). None of the individuals had epilepsy or hearing loss. Individuals were from Saudi Arabian, Malay, European and Native American ethnicities. 5 different variants were reported including nonsense, frameshift and splice donor variants. In family A a heterozygous ABCA3 missense variant of unknown significance was also inherited from the mother. Biallelic variants in ABCA3 are associated with Surfactant metabolism dysfunction, pulmonary, 3, OMIM:610921. The authors report that while there are 53 TMEM63B pLoF variants in gnomAD v.4.1.0 database none are in the homozygous state. Histopathological examination of lung tissue also showed a pattern consistent with surfactant dysfunction. The authors conclude that biallelic loss of function variants result in a distinct pulmonary-predominant phenotype characterized by hypoxemia, early-onset respiratory failure, histological features of surfactant dysfunction, and chest imaging consistent with chILD. |
|||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v2.106 | TMEM63B | Eleanor Williams reviewed gene: TMEM63B: Rating: GREEN; Mode of pathogenicity: None; Publications: 37421948, 42259295, doi:10.1016/j.bdcasr.2024.100043; Phenotypes: Developmental and epileptic encephalopathy 118, MIM:621250, autosomal-recessive TMEM63B-related syndromic surfactant dysfunction disorder; Mode of inheritance: BOTH monoallelic and biallelic, autosomal or pseudoautosomal | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v2.0 | CASR | Gene migrated from ENSG00000036828 to ENSG00000036828 (gene set migration) | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.12503 | CASR | Ain Roesley Marked gene: CASR as ready | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.12503 | CASR | Ain Roesley Gene: casr has been classified as Green List (High Evidence). | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.12503 | CASR | Ain Roesley Phenotypes for gene: CASR were changed from to Hyperparathyroidism, neonatal MIM#239200; Hypocalcemia, autosomal dominant MIM#601198; Hypocalcemia autosomal dominant, with Bartter syndrome MIM#601198; hypercalcemia, type I MIM#145980 | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.12502 | CASR | Ain Roesley Publications for gene: CASR were set to | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.12502 | CASR | Ain Roesley Mode of inheritance for gene: CASR was changed from Unknown to BOTH monoallelic and biallelic (but BIALLELIC mutations cause a more SEVERE disease form), autosomal or pseudoautosomal | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.12501 | CASR | Ain Roesley reviewed gene: CASR: Rating: GREEN; Mode of pathogenicity: None; Publications: 7916660, 7726161, 8675635, 17698911, 22620673, 26646938, 22422767; Phenotypes: Hyperparathyroidism, neonatal MIM#239200, Hypocalcemia, autosomal dominant MIM#601198, Hypocalcemia autosomal dominant, with Bartter syndrome MIM#601198, hypercalcemia, type I MIM#145980; Mode of inheritance: BOTH monoallelic and biallelic (but BIALLELIC mutations cause a more SEVERE disease form), autosomal or pseudoautosomal; Current diagnostic: yes | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.0 | CASR |
Zornitza Stark gene: CASR was added gene: CASR was added to Mendeliome_VCGS. Sources: Expert Review Green,Victorian Clinical Genetics Services Mode of inheritance for gene: CASR was set to Unknown |
|||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||