Etiqueta: AmJHumGenet
-
Landscape of parental postzygotic mutations across >11,000 rare disease trios
Garcia-Salinas et al. detect early parental postzygotic mutations from standard-depth trio WGS across 12,015 rare disease trios, identifying 1,015 high-confidence events. Their catalog reveals distinct mutational features of early embryonic mutagenesis…
-
Likelihood-based calibration improves the clinical utility of JAG1 functional data for variant classification
We translate JAG1 functional data obtained from a multiplexed assay of variant effects (MAVE) into ACMG/AMP-compatible log-likelihood evidence, improving variant interpretation in Alagille syndrome. This calibration enhances benign/pathogenic separatio…
-
Landscape of parental postzygotic mutations across >11,000 rare disease trios
Garcia-Salinas et al. detect early parental postzygotic mutations from standard-depth trio WGS across 12,015 rare disease trios, identifying 1,015 high-confidence events. Their catalog reveals distinct mutational features of early embryonic mutagenesis…
-
Likelihood-based calibration improves the clinical utility of JAG1 functional data for variant classification
We translate JAG1 functional data obtained from a multiplexed assay of variant effects (MAVE) into ACMG/AMP-compatible log-likelihood evidence, improving variant interpretation in Alagille syndrome. This calibration enhances benign/pathogenic separatio…
-
Clinical, in vitro, and in vivo evidence of WAPL as a cohesinopathy-associated gene and phenotypic driver of 10q22.3q23.2 genomic disorder
Boone et al. describe a neurodevelopmental condition caused by haploinsufficiency of the cohesin release factor WAPL and provide phenotypic and functional genomic evidence of WAPL as a driver gene within the 10q22.3q23.2 genomic disorder region.
-
Clinical, in vitro, and in vivo evidence of WAPL as a cohesinopathy-associated gene and phenotypic driver of 10q22.3q23.2 genomic disorder
Boone et al. describe a neurodevelopmental condition caused by haploinsufficiency of the cohesin release factor WAPL and provide phenotypic and functional genomic evidence of WAPL as a driver gene within the 10q22.3q23.2 genomic disorder region.
-
Overlapping Xp21.2 duplications define an X-linked hypotrichosis simplex and implicate TAB3 dosage sensitivity
Overlapping Xp21.2 duplications define a previously unrecognized X-linked hypotrichosis simplex driven by increased TAB3 dosage. Functional studies demonstrate that TAB3 overexpression perturbs TAK1-NF-κB signaling, induces inflammatory skin abnormalit…
-
Overlapping Xp21.2 duplications define an X-linked hypotrichosis simplex and implicate TAB3 dosage sensitivity
Overlapping Xp21.2 duplications define a previously unrecognized X-linked hypotrichosis simplex driven by increased TAB3 dosage. Functional studies demonstrate that TAB3 overexpression perturbs TAK1-NF-κB signaling, induces inflammatory skin abnormalit…
-
Bi-allelic variants in CDK20 cause a severe ciliopathy with midline brain and facial anomalies
CDK20 is a ciliary kinase not previously linked to human disease. Lemire et al. report seven individuals with bi-allelic CDK20 variants, midline brain and facial anomalies, and impaired cilium formation and Hedgehog responsiveness, establishing CDK20 l…
-
Bi-allelic variants in CDK20 cause a severe ciliopathy with midline brain and facial anomalies
CDK20 is a ciliary kinase not previously linked to human disease. Lemire et al. report seven individuals with bi-allelic CDK20 variants, midline brain and facial anomalies, and impaired cilium formation and Hedgehog responsiveness, establishing CDK20 l…