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| Mendeliome v1.2698 | BHLHA9 | Zornitza Stark Tag SV/CNV tag was added to gene: BHLHA9. | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v1.2697 | BHLHA9 |
Sarah Milton changed review comment from: BHLHA9 encodes a transcription factor involved in embryonic limb development, essential for interdigital apoptosis in central limb mesenchyme cells. Duplications encompassing a 11.8kb critical region involving BHLHA9 have been reported in a number of publications to result in split hand foot malformation with long bone deficiency in at least 50 affected individuals. This has segregated within families of affected individuals on a number of occasions. However, penetrance of approximately 50% has been noted with significant intrafamilial variability. It should also be noted that in gnomad v4 structural variants there are 15 dups encompassing this same region in het individuals with a DGV gold track demonstrating dups in 3 individuals. Duan et al 2022 (PMID: 36035248) proposed copy number gains might enhance the regulatory potential as a transcription factor; thus, the apoptosis activity may be overly or ectopically increased in central limb mesenchymal cells during limb development. Authors proposed a gene dosage change with increasing copies of BHLHA9 showing increasing penetrance using examples of individuals with homozygous duplications or heterozygous triplications.; to: BHLHA9 encodes a transcription factor involved in embryonic limb development, essential for interdigital apoptosis in central limb mesenchyme cells. Duplications encompassing a 11.8kb critical region involving BHLHA9 have been reported in a number of publications to result in split hand foot malformation with long bone deficiency in at least 50 affected individuals. This has segregated within families of affected individuals on a number of occasions. However, penetrance of approximately 50% has been noted with significant intrafamilial variability. It should also be noted that in gnomad v4 structural variants there are 15 dups encompassing this same region in het individuals with a DGV gold track demonstrating dups in 3 individuals. Duan et al 2022 (PMID: 36035248) proposed copy number gains might enhance the regulatory potential as a transcription factor; thus, the apoptotic activity may be overly or ectopically increased in central limb mesenchymal cells during limb development. Authors proposed a gene dosage change with increasing copies of BHLHA9 showing increasing penetrance using examples of individuals with homozygous duplications or heterozygous triplications. |
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| Mendeliome v1.2697 | BHLHA9 |
Sarah Milton changed review comment from: BHLHA9 encodes a transcription factor involved in embryonic limb development, essential for interdigital apoptosis in central limb mesenchyme cells. Duplications encompassing a 11.8kb critical region involving BHLHA9 have been reported in a number of publications to result in split hand foot malformation with long bone deficiency in at least 50 affected individuals. This has segregated in affected families on a number of occasions. However, penetrance of approximately 50% has been noted with significant intrafamilial variability. It should also be noted that in gnomad v4 structural variants there are 15 dups encompassing this same region in het individuals with a DGV gold track demonstrating dups in 3 individuals. Duan et al 2022 (PMID: 36035248) proposed copy number gains might enhance the regulatory potential as a transcription factor; thus, the apoptosis activity may be overly or ectopically increased in central limb mesenchymal cells during limb development. Authors proposed a gene dosage change with increasing copies of BHLHA9 showing increasing penetrance using examples of individuals with homozygous duplications or heterozygous triplications.; to: BHLHA9 encodes a transcription factor involved in embryonic limb development, essential for interdigital apoptosis in central limb mesenchyme cells. Duplications encompassing a 11.8kb critical region involving BHLHA9 have been reported in a number of publications to result in split hand foot malformation with long bone deficiency in at least 50 affected individuals. This has segregated within families of affected individuals on a number of occasions. However, penetrance of approximately 50% has been noted with significant intrafamilial variability. It should also be noted that in gnomad v4 structural variants there are 15 dups encompassing this same region in het individuals with a DGV gold track demonstrating dups in 3 individuals. Duan et al 2022 (PMID: 36035248) proposed copy number gains might enhance the regulatory potential as a transcription factor; thus, the apoptosis activity may be overly or ectopically increased in central limb mesenchymal cells during limb development. Authors proposed a gene dosage change with increasing copies of BHLHA9 showing increasing penetrance using examples of individuals with homozygous duplications or heterozygous triplications. |
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| Mendeliome v1.2697 | BHLHA9 | Sarah Milton reviewed gene: BHLHA9: Rating: GREEN; Mode of pathogenicity: Loss-of-function variants (as defined in pop up message) DO NOT cause this phenotype - please provide details in the comments; Publications: PMID: 22147889, 23790188, 29970136, 31200655, 36035248, 36028842, 36551834; Phenotypes: Split-hand/foot malformation with long bone deficiency 3 MIM#612576; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.9670 | BHLHA9 | Zornitza Stark Marked gene: BHLHA9 as ready | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.9670 | BHLHA9 | Zornitza Stark Gene: bhlha9 has been classified as Green List (High Evidence). | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.9670 | BHLHA9 | Zornitza Stark Phenotypes for gene: BHLHA9 were changed from to Syndactyly, mesoaxial synostotic, with phalangeal reduction, MIM# 609432 | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.9669 | BHLHA9 | Zornitza Stark Publications for gene: BHLHA9 were set to | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.9668 | BHLHA9 | Zornitza Stark Mode of inheritance for gene: BHLHA9 was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.9667 | BHLHA9 | Zornitza Stark reviewed gene: BHLHA9: Rating: GREEN; Mode of pathogenicity: None; Publications: 25466284, 34272776, 31912643, 31152918, 30107244; Phenotypes: Syndactyly, mesoaxial synostotic, with phalangeal reduction, MIM# 609432; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.0 | BHLHA9 |
Zornitza Stark gene: BHLHA9 was added gene: BHLHA9 was added to Mendeliome_VCGS. Sources: Expert Review Green,Victorian Clinical Genetics Services Mode of inheritance for gene: BHLHA9 was set to Unknown |
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