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Mendeliome v1.4850 CHCHD4 Zornitza Stark Marked gene: CHCHD4 as ready
Mendeliome v1.4850 CHCHD4 Zornitza Stark Gene: chchd4 has been classified as Red List (Low Evidence).
Mendeliome v1.4850 CHCHD4 Zornitza Stark Phenotypes for gene: CHCHD4 were changed from IUGR; lactic acidosis; liver disease; hypoglycaemia; dystonia; hypertonia; regression to Mitochondrial disease, MONDO:0044970, CHCHD4-related
Mendeliome v1.4849 CHCHD4 Zornitza Stark Classified gene: CHCHD4 as Red List (low evidence)
Mendeliome v1.4849 CHCHD4 Zornitza Stark Gene: chchd4 has been classified as Red List (Low Evidence).
Mendeliome v1.4848 CHCHD4 Zornitza Stark reviewed gene: CHCHD4: Rating: RED; Mode of pathogenicity: None; Publications: ; Phenotypes: Mitochondrial disease, MONDO:0044970, CHCHD4-related; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Mendeliome v1.4844 CHCHD4 Isabelle Adant gene: CHCHD4 was added
gene: CHCHD4 was added to Mendeliome. Sources: Literature
Mode of inheritance for gene: CHCHD4 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: CHCHD4 were set to 41981912; 26004228
Phenotypes for gene: CHCHD4 were set to IUGR; lactic acidosis; liver disease; hypoglycaemia; dystonia; hypertonia; regression
Review for gene: CHCHD4 was set to RED
Added comment: 41981912
1 individual compound heterozygous for missense variant and large deletion
encompassing the whole CHCHD4 gene (and adjacent gene) of biparental inheritance,
presenting with IUGR, liver dysfunction, lactic acidosis and short-fasting
hypoglycaemia, developmental delay and regression, hypertonia and
dystonia. Early demise at 11months.
Minimal supporting biochemical evidence (protein expression studies) in patient-derived fibroblasts.

26004228 : Chchd4−/− mouse model
Biallelic Chchd4 in mouse embryos causes a developmental arrest coupled
with embryonic lethality at the onset of gastrulation. The developmental
retardation of Chchd4−/− embryos was accompanied by a major defect in the
expression of respiratory chain complex I subunit CI-20.
Sources: Literature
Mendeliome v1.941 CHD4 Achchuthan Shanmugasundram changed review comment from: This gene should be added to the Clefting disorders panel with a green rating as there are four unrelated cases presenting with either cleft palate and/or bifid uvula.

PMID:3138819 reported a patient with heterozygous variant (p.Gln715Ter) in CHD4 that had cleft palate and pierre robin. In addition, another patient identified with heterozygous variant p.Arg1127Gln was reported with bifid uvula.

In addition, DDD study reported two patients with likely pathogenic heterozygous variants who had cleft palate in addition to several other clinical presentations including global developmental delay (PMID:37010288); to: Although there are four unrelated cases presenting with either cleft palate and/or bifid uvula, this phenotype is not consistent among patients identified with monoallelic variants in CHD4 gene. Hence, this gene should be added to the Clefting disorders panel with amber rating.

PMID:31388190 reported 32 patients with heterozygous variants in CHD4 gene, of which one patient (p.Gln715Ter) had cleft palate and pierre robin. In addition, another patient identified with heterozygous variant p.Arg1127Gln was reported with bifid uvula.

In addition, 2 out of 10 patients with pathogenic/ likely pathogenic heterozygous variants from the DDD study were reported with cleft palate in addition to several other clinical presentations including global developmental delay (PMID:37010288).
Mendeliome v1.941 CHD4 Achchuthan Shanmugasundram edited their review of gene: CHD4: Changed rating: AMBER
Mendeliome v1.939 CHD4 Achchuthan Shanmugasundram reviewed gene: CHD4: Rating: GREEN; Mode of pathogenicity: None; Publications: 31388190, 37010288; Phenotypes: Sifrim-Hitz-Weiss syndrome, OMIM:617159; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Mendeliome v1.879 GATAD2A Bryony Thompson changed review comment from: https://doi.org/10.1016/j.xhgg.2023.100198 - Five unrelated individuals with a neurodevelopmental disorder identified with 3 missense & 2 LoF (4 de novo & 1 unknown inheritance). The shared clinical features with variable expressivity include global developmental delay (4/4), craniofacial dysmorphism (3/5), structural brain defects (2/3), musculoskeletal anomalies (3/5), vision/hearing defects (2/3), gastrointestinal/renal defects (2/3). Loss of function is the expected mechanism of disease. In vitro assays of one of the missense variants (p.Cys420Tyr) demonstrates disruption of GATAD2A integration with CHD3, CHD4, and CHD5
PMID: 17565372 - null mouse model is embryonic lethal.
Sources: Literature; to: PMID: 37181331 - Five unrelated individuals with a neurodevelopmental disorder identified with 3 missense & 2 LoF (4 de novo & 1 unknown inheritance). The shared clinical features with variable expressivity include global developmental delay (4/4), craniofacial dysmorphism (3/5), structural brain defects (2/3), musculoskeletal anomalies (3/5), vision/hearing defects (2/3), gastrointestinal/renal defects (2/3). Loss of function is the expected mechanism of disease. In vitro assays of one of the missense variants (p.Cys420Tyr) demonstrates disruption of GATAD2A integration with CHD3, CHD4, and CHD5
PMID: 17565372 - null mouse model is embryonic lethal.
Sources: Literature
Mendeliome v1.830 GATAD2A Bryony Thompson gene: GATAD2A was added
gene: GATAD2A was added to Mendeliome. Sources: Literature
Mode of inheritance for gene: GATAD2A was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: GATAD2A were set to https://doi.org/10.1016/j.xhgg.2023.100198; 17565372
Phenotypes for gene: GATAD2A were set to Neurodevelopmental disorder, MONDO:0700092, GATAD2A-related
Review for gene: GATAD2A was set to GREEN
Added comment: https://doi.org/10.1016/j.xhgg.2023.100198 - Five unrelated individuals with a neurodevelopmental disorder identified with 3 missense & 2 LoF (4 de novo & 1 unknown inheritance). The shared clinical features with variable expressivity include global developmental delay (4/4), craniofacial dysmorphism (3/5), structural brain defects (2/3), musculoskeletal anomalies (3/5), vision/hearing defects (2/3), gastrointestinal/renal defects (2/3). Loss of function is the expected mechanism of disease. In vitro assays of one of the missense variants (p.Cys420Tyr) demonstrates disruption of GATAD2A integration with CHD3, CHD4, and CHD5
PMID: 17565372 - null mouse model is embryonic lethal.
Sources: Literature
Mendeliome v0.9324 CHD4 Zornitza Stark Phenotypes for gene: CHD4 were changed from Sifrim-Hitz-Weiss syndrome, MIM 617159 to Sifrim-Hitz-Weiss syndrome, MIM 617159; Childhood idiopathic epilepsy and sinus arrhythmia
Mendeliome v0.9323 CHD4 Zornitza Stark Publications for gene: CHD4 were set to 31388190
Mendeliome v0.9322 CHD4 Zornitza Stark reviewed gene: CHD4: Rating: GREEN; Mode of pathogenicity: None; Publications: 34109749; Phenotypes: Childhood idiopathic epilepsy and sinus arrhythmia; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Mendeliome v0.2518 CHD4 Zornitza Stark Marked gene: CHD4 as ready
Mendeliome v0.2518 CHD4 Zornitza Stark Gene: chd4 has been classified as Green List (High Evidence).
Mendeliome v0.2518 CHD4 Zornitza Stark Phenotypes for gene: CHD4 were changed from to Sifrim-Hitz-Weiss syndrome, MIM 617159
Mendeliome v0.2517 CHD4 Zornitza Stark Publications for gene: CHD4 were set to
Mendeliome v0.2516 CHD4 Zornitza Stark Mode of inheritance for gene: CHD4 was changed from Unknown to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Mendeliome v0.2406 CHD4 Teresa Zhao reviewed gene: CHD4: Rating: GREEN; Mode of pathogenicity: None; Publications: PMID:31388190; Phenotypes: Sifrim-Hitz-Weiss syndrome, MIM 617159; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown; Current diagnostic: yes
Mendeliome v0.0 CHD4 Zornitza Stark gene: CHD4 was added
gene: CHD4 was added to Mendeliome_VCGS. Sources: Expert Review Green,Victorian Clinical Genetics Services
Mode of inheritance for gene: CHD4 was set to Unknown