Case#: Patient 1, male, Russian

DiseaseAssertion: MPS1-H

FamilyInfo: N/A

CasePresentingHPOs: Severe intellectual disability, corneal clouding, skeletal deformities, hepatosplenomegaly (HP:0010864, HP:0007957, HP:0000924, HP:0001433)

CaseHPOFreeText: N/A

CaseNotHPOs: N/A

CaseNotHPOFreeText: N/A

CaseEnzymeAssay: 4.5 nmol/mg/h (reference range 135 ± 57 nmol/mg/h)

CaseUrineGAGs: 42.9 mg GAG/mmol/creatinine (reference range 6.17 ± 3.79 mg GAG/mmol creatinine)

CaseERT: No

CaseBMT: No

Variant1: c.208C>T (p.Q70X)

Variant1ClinVarID: 11909

Variant1CAID: CA204563

Variant2: c.974insACCCCCATTTAC (p.Thr293_Tyr296dup) - in ClinVar this variant is listed as c.878_889dup12.

Variant2ClinVarID: 550382

Variant2CAID: CA2802114

AdditionalVariants: N/A

ParentalGenotype: N/A

PreviouslyPublished N/A

Case#: Family 16, Italy

DiseaseAssertion: MPS1-H

FamilyInfo: N/A

CasePresentingHPOs: N/A

CaseHPOFreeText: The paper states that "Hurler form is characterized by skeletal abnormalities, hepatosplenomegaly and severe mental retardation" but is not specific to this patient.

CaseNotHPOs: N/A

CaseNotHPOFreeText: N/A

CaseEnzymeAssay: The α-L-iduronidase enzyme activities in leucocytes from all patients in the study was measured using the artificial substrate 4-methylumbelliferyl α-L iduronide (Sigma). Values ranged from 0 to 2.47 nmol/h/mg protein (reference range: 28–92 nmol/h/mg protein) and did not correlate to the clinical phenotype.

α-L-iduronidase activity in COS-7 cells transiently transfected with wild-type or mutagenised cDNAs. α-L-iduronidase activity: 4.9 nmol/h/mg cell protein (p.P496R), 99.3 nmol/h/mg cell protein (p.A591T); values are the means of two experiments.

CaseUrineGAGs: N/A

CaseERT: N/A

CaseBMT: N/A

Variant1: c.878_889dup (p.Thr293_Tyr296dup); c.974ins12 in the paper (old nomenclature

Variant1ClinVarID: 550382

Variant1CAID: CA2802114

Variant2: c.1487C>G (p.P496R)

Variant2ClinVarID: 496861

Variant2CAID: CA2802275

AdditionalVariants: 1771G>A (p.A591T) The polymorphism and novel missense mutations were transiently expressed in COS-7 cells and all of them except the polymorphism showed complete loss of enzyme activity.

ParentalGenotype: N/A

PreviouslyPublished N/A

Case#: 0.9% residual activity at 37 °C

DiseaseAssertion: MPS1-S

FamilyInfo: N/A

CasePresentingHPOs: N/A

CaseHPOFreeText: N/A

CaseNotHPOs: N/A

CaseNotHPOFreeText: N/A

CaseEnzymeAssay: 2.5 ± 0.2 nmol/mg/h IDUA activity at 37 °C

CaseUrineGAGs: N/A

CaseERT: N/A

CaseBMT: N/A

Variant1: c.1861C>T (p.R621X)

Variant1ClinVarID: 11917

Variant1CAID: CA256118

Variant2: c.974ins12 in paper but nomenclature is c.878_889dup (p.Thr293_Tyr296dup)

ClinVarID: 550382

Variant2CAID: CA2802114

AdditionalVariants: N/A

ParentalGenotype: N/A

PreviouslyPublished N/A

Case#: Patient 29, Italy

DiseaseAssertion: MPS1-S

FamilyInfo: N/A

CasePresentingHPOs: N/A

CaseHPOFreeText: N/A

CaseNotHPOs: N/A

CaseNotHPOFreeText: N/A

CaseEnzymeAssay: N/A

CaseUrineGAGs: N/A

CaseERT: N/A

CaseBMT: N/A

Variant1: c.979G>C (p.A327P)

Variant1ClinVarID: 167190

Variant1CAID: CA234128

Variant2: c.878_889dup

Variant2ClinVarID: 550382

Variant2CAID: CA2802114

AdditionalVariants: N/A

ParentalGenotype: N/A

PreviouslyPublished N/A

Case#: Patient 49, Poland

DiseaseAssertion: MPS1-S

FamilyInfo: N/A

CasePresentingHPOs: N/A

CaseHPOFreeText: N/A

CaseNotHPOs: N/A

CaseNotHPOFreeText: N/A

CaseEnzymeAssay: N/A

CaseUrineGAGs: N/A

CaseERT: N/A

CaseBMT: N/A

Variant1: c.878_889dup (p.Thr293_Tyr296dup)

Variant1ClinVarID: 550382

Variant1CAID: CA2802114

Variant2: c.1181_1189dup (p.Ala394_Leu396dup)

Variant2ClinVarID: 3720561

Variant2CAID: CA549264540

AdditionalVariants: N/A

ParentalGenotype: N/A

PreviouslyPublished N/A