CaseBI2K: N/A

CasePresentingHPOs: HP:0001875, HP:0001644, HP:0003756 (Neutropenia, Dilated cardiomyopathy, Skeletal myopathy)

HPOsFreeText: N/A

CaseNotHPOs: N/A

NotHPOsFreeText: N/A

CaseGenotypingMethod: Five genes noted to have high heart and skeletal muscle expression were sequenced and ORFs created. After PCR amplification and direct sequencing of the TAZ gene (G4.5.), a unique missense variant was found in this proband.

CasePreviousTesting: N/A

CaseAddInfo: N/A

Variant: NM_000116.5(TAZ):c.239-1G>C

ClinVar: 11102, https://www.ncbi.nlm.nih.gov/clinvar/variation/11102/

gnomAD: Not in gnomAD

FamilyRO: N/A

FamilyPresentingHPOs: HP:0001252, HP:0001635, HP:0012664, HP:0001875, HP:0001640, HP:0001324 (Muscular hypotonia, Congestive heart failure, Reduced ejection fraction, Neutropenia, Cardiomegaly, Muscle weakness)

HPOsFreeText: N/A

FamilyNotHPOs: N/A

NotHPOsFreeText: N/A

FamilyGenotypingMethod: DNA was extracted from salavia and buccal swabs. DNA sequencing for all 11 exons of the TAZ gene was performed via PCR amplification and direct sequencing. Once the mutation was located, site-specific DNA sequencing was used on four unaffected family members to confirm segregation.

FamilyPreviousTesting: N/A

FamilyAddInfo: N/A

Variant: NM_000116.5(TAZ):c.583G>T (p.Gly195Ter)

ClinVar: 559336, https://www.ncbi.nlm.nih.gov/clinvar/variation/559336/

gnomAD: Not in gnomAD

Affected: 2

Unaffected: 2

Segregations: 4

AddSegregationInfo: Not enough info to count, pedigree in Figure 1

CaseDO2: Male, Italy, 1 day onset

CasePresentingHPOs: HP:0001252, HP:0002045, HP:0002033, HP:0001958, HP:0001987, HP:0002151, HP:0001942, HP:0003648, HP:0001640, HP:0001644, HP:0001667, HP:0003324, HP:0001270, HP:0001510, HP:0001875, HP:0002098, HP:0001649, HP:0000969, HP:0001712, HP:0012666, HP:0003535, HP:0001397, HP:0001706 (Muscular hypotonia, Hypothermia, Poor suck, Nonketotic hypoglycemia, Hyperammonemia, Increased serum lactate, Metabolic acidosis, Lacticaciduria, Cardiomegaly, Dilated cardiomyopathy, Right ventricular hypertrophy, Generalized muscle weakness, Motor delay, Growth delay, Neutropenia, Respiratory distress, Tachycardia, Edema, Left ventricular hypertrophy, Severely reduced ejection fraction, 3-Methylglutaconic aciduria, Hepatic steatosis, Endocardial fibroelastosis)

HPOsFreeText: N/A

CaseNotHPOs: HP:0001875 (Neutropenia)

NotHPOsFreeText: N/A

CaseAddInfo: N/A

CasePreviousTesting: Birth weight of 2830 g; Unremarkable family history; See "Results" for exact metabolic values

CaseGenotypingMethod: Genomic DNA was isolated from whole blood and the TAZ gene was amplified and directly sequenced.

Variant: NM_000116.4:c.541+1G>A

CAID: CA415183775, http://reg.clinicalgenome.org/redmine/projects/registry/genboree_registry/by_caid?caid=CA415183775

gnomAD: Not in gnomAD

CaseDO1: Male, Italy, 3 days onset

CasePresentingHPOs: HP:0011968, HP:0001254, HP:0001252, HP:0002045, HP:0001640, HP:0012664, HP:0002119, HP:0001943, HP:0002910, HP:0003236, HP:0001942, HP:0002151, HP:0003542, HP:0100493, HP:0008315, HP:0011936, HP:0003648, HP:0003344, HP:0003535, HP:0001508, HP:0001270, HP:0001649, HP:0001875, HP:0001644, HP:0002375, HP:0001706, HP:0001397 (Poor feeding, Lethargy, Muscular hypotonia, Hypothermia, Cardiomegaly, Reduced ejection fraction, Ventriculomegaly, Hypoglycemia, Elevated hepatic transaminase, Elevated serum creatine kinase, Metabolic acidosis, Increased serum lactate, Increased serum pyruvate, Hypoammonemia, Decreased plasma free carnitine, Decreased plasma total carnitine, Lacticaciduria, 3-Methylglutaric aciduria, 3-Methylglutaconic aciduria, Failure to thrive, Motor delay, Tachycardia, Neutropenia, Dilated cardiomyopathy, Hypokinesia, Endocardial fibroelastosis, Hepatic steatosis)

HPOsFreeText: N/A

CaseNotHPOs: HP:0002240, HP:0002919 (Hepatomegaly, Ketonuria)

NotHPOsFreeText: N/A

CaseAddInfo: N/A

CasePreviousTesting: Birth weight of 2780 g; Three maternal great-uncles and two maternal second cousins died in the first years of life; See "Results" for exact metabolic values;

CaseGenotypingMethod: Genomic DNA was isolated from whole blood and the TAZ gene was amplified and directly sequenced.

Variant: NM_000116.5(TAZ):c.589G>A (p.Gly197Arg)

ClinVar: 11105, https://www.ncbi.nlm.nih.gov/clinvar/variation/11105/

gnomAD: Not in gnomAD

CaseCA5: Male, 9 months death

CasePresentingHPOs: HP:0001644, HP:0001875, HP:0001508, HP:0003535, HP:0002014, HP:0008872, HP:0003146 (Dilated cardiomyopathy, Neutropenia, Failure to thrive, 3-Methylglutaconic aciduria, Diarrhea, Feeding difficulties in infancy, Hypocholesterolemia)

HPOsFreeText: N/A

CaseNotHPOs: N/A

NotHPOsFreeText: N/A

CaseAddInfo: N/A

CasePreviousTesting: N/A

CaseGenotypingMethod: The TAZ gene was PCR amplified in three fragments and directly sequenced in the mother and proband.

Variant: NM_000116.4:c.629T>G (p.Leu210Arg)

CAID: CA415184340, http://reg.clinicalgenome.org/redmine/projects/registry/genboree_registry/by_caid?caid=CA415184340

gnomAD: Not in gnomAD

CaseCA3: Male, 6 months diagnosis

CasePresentingHPOs: HP:0001644, HP:0001875, HP:0001508, HP:0003535, HP:0003756, HP:0030319, HP:0003551 (Dilated cardiomyopathy, Neutropenia, Failure to thrive, 3-Methylglutaconic aciduria, Skeletal myopathy, Facial weakness, Difficulty climbing stairs)

HPOsFreeText: N/A

CaseNotHPOs: HP:0003107 (Abnormal circulating cholesterol concentration)

NotHPOsFreeText: N/A

CaseAddInfo: Cardiac transplant 11 months after presentation; Variant also found in mother and grandmother

CasePreviousTesting: N/A

CaseGenotypingMethod: The TAZ gene was PCR amplified in three fragments and directly sequenced in the mother and proband.

Variant: NM_000116.5(TAZ):c.589G>A (p.Gly197Arg)

ClinVar: 11105, https://www.ncbi.nlm.nih.gov/clinvar/variation/11105/

gnomAD: Not in gnomAD

CaseCA3: Male, 6 months diagnosis

CasePresentingHPOs: HP:0001644, HP:0001875, HP:0001508, HP:0003535, HP:0003756, HP:0030319, HP:0003551 (Dilated cardiomyopathy, Neutropenia, Failure to thrive, 3-Methylglutaconic aciduria, Skeletal myopathy, Facial weakness, Difficulty climbing stairs)

HPOsFreeText: N/A

CaseNotHPOs: HP:0003107 (Abnormal circulating cholesterol concentration)

NotHPOsFreeText: N/A

CaseAddInfo: Cardiac transplant 11 months after presentation; Variant also found in mother and grandmother

CasePreviousTesting: N/A

CaseGenotypingMethod: The TAZ gene was PCR amplified in three fragments and directly sequenced in the mother and proband.

Variant: NM_000116.5(TAZ):c.589G>A (p.Gly197Arg)

ClinVar: 11105, https://www.ncbi.nlm.nih.gov/clinvar/variation/11105/

gnomAD: Not in gnomAD