Case#: Patient W3, 10 years old, Chinese. The patient had normal intelligence based on their performance in school.

DiseaseAssertion: MPS1-H/S

FamilyInfo: Patient received the p.M1I mutation from their mother and received the p.Y343X from their father.

CasePresentingHPOs: Short stature, coarse facial features, severe skeletal deformities (HP:0004322, HP:0000280, HP:0000924)

CaseHPOFreeText: N/A

CaseNotHPOs: N/A

CaseNotHPOFreeText: N/A

CaseEnzymeAssay: Expression of Y343X in COS-7 cells showed retention of a very low level of IDUA activity

CaseUrineGAGs: N/A

CaseERT: N/A

CaseBMT: N/A

Variant1: c.3G>A (p.M1I)

Variant1ClinVarID: 557150

Variant1CAID: CA355945212

Variant2: c.1029C>A (p.Y343X)

Variant2ClinVarID: 222997

Variant2CAID: CA356984

AdditionalVariants: The patient has one IDUA allele with the variant c.3G>A (p.M1I) and an in frame deletion of the whole of exon 2, whereas the other allele has Y343X (an in frame deletion of nucleotides 1061-1117 in exon 8).

ParentalGenotype: Maternal - p.M1I, Paternal - p.Y343X

PreviouslyPublished N/A

This paper is cited on the ClinVar page for this variant, but this is actually the c.1029C>G (p.Tyr343Ter) variant which causes the same amino acid change

Case#: Severe MPS1 patients

DiseaseAssertion: Severe MPS I

FamilyInfo: n/a, "neither the laboratory method used to determine the sequence variants nor whether parental testing confirmed the inheritance or phase of the variants is captured by the Registry"

CasePresentingHPOs:

CaseHPOFreeText: "All patients enrolled in the Registry have confirmation of MPS I diagnosis by either mutation analysis or measurement of IDUA levels."

CaseNotHPOs:

CaseNotHPOFreeText:

CasePreviousTesting: n/a

GenotypingMethod: n/a

PreviouslyPublished: possible since this is a multinational registry

Variant: Q70X/Y343X

ClinVar: 222997

CAID: CA356984

SupplementalData: Table S1 has the genotypes listed

Case#: Patient 4, 11 years old, Iranian

DiseaseAssertion: MPS1-H (Severe)

FamilyInfo: N/A

CasePresentingHPOs: N/A

CaseHPOFreeText: N/A

CaseNotHPOs: N/A

CaseNotHPOFreeText: N/A

CaseEnzymeAssay: IDUA activity not detected

CaseUrineGAGs: N/A

CaseERT: N/A

CaseBMT: N/A

Variant1: c.1029C>A (p.Y343X)

Variant1ClinVarID: 222997

Variant1CAID: CA356984

Variant2: c.1029C>A (p.Y343X)

Variant2ClinVarID: 222997

Variant2CAID: CA356984

AdditionalVariants: N/A

ParentalGenotype: N/A

PreviouslyPublished N/A

Case#: Patient 4, 11 years old, Iranian

DiseaseAssertion: MPS1-H (Severe)

FamilyInfo: N/A

CasePresentingHPOs: N/A

CaseHPOFreeText: N/A

CaseNotHPOs: N/A

CaseNotHPOFreeText: N/A

CaseEnzymeAssay: IDUA activity not detected

CaseUrineGAGs: N/A

CaseERT: N/A

CaseBMT: N/A

Variant1: c.1029C>A (p.Y343X)

Variant1ClinVarID: 222997

Variant1CAID: CA356984

Variant2: c.1029C>A (p.Y343X)

Variant2ClinVarID: 222997

Variant2CAID: CA356984

AdditionalVariants: N/A

ParentalGenotype: N/A

PreviouslyPublished N/A

Case#: Patient 23, 9 months old (age at report), female, Indian

DiseaseAssertion: MPS1-H

FamilyInfo: N/A

CasePresentingHPOs: Intellectual disability (HP:0001249)

CaseHPOFreeText: N/A

CaseNotHPOs: N/A

CaseNotHPOFreeText: N/A

CaseEnzymeAssay: 0.0% (Range of residual enzyme activity: 0.0%-4.8%)

CaseUrineGAGs: N/A

CaseERT: N/A

CaseBMT: N/A

Variant1: c.1029C>A (p.Tyr353Ter)

Variant1ClinVarID: 222997

Variant1CAID: CA356984

Variant2: c.1029C>A (p.Tyr353Ter)

Variant2ClinVarID: 222997

Variant2CAID: CA356984

AdditionalVariants: N/A

ParentalGenotype: N/A

PreviouslyPublished N/A

Case#: Patient 109, Far East district of the Russian Federation

DiseaseAssertion: MPS1, Severe

FamilyInfo:

CasePresentingHPOs:

CaseHPOFreeText: IdA activity in DBS=0,01 leukocytes, severe phenotype, hyperexcretion of urine heparan and dermatan sulfate

CaseNotHPOs:

CaseNotHPOFreeText:

CasePreviousTesting: Electrophoresis of urine GAGs and measurement of lysosomal enzyme activity in peripheral blood leukocytes or DBSs were performed for all patients with suspected MPS I

GenotypingMethod: The 14 exons and exon–intron boundaries of the IDUA gene were amplified from DNA samples. Sanger sequencing of each one of the 14 exons was performed. PCR products containing mutations were re-sequenced in both directions. The mutations were further confirmed where possible by restriction analysis (data not shown).

PreviouslyPublished:

Variant: NM_000203.5:c.[208C>T];[1029C>A]

ClinVar: 222997

CAID: CA356984

SupplementalData: n/a

Case#: Patient 108, Central district of the Russian Federation

DiseaseAssertion: MPS1, Severe

FamilyInfo:

CasePresentingHPOs:

CaseHPOFreeText: IdA activity in DBS=0,01 DBS, severe phenotype, hyperexcretion of urine heparan and dermatan sulfate

CaseNotHPOs:

CaseNotHPOFreeText:

CasePreviousTesting: Electrophoresis of urine GAGs and measurement of lysosomal enzyme activity in peripheral blood leukocytes or DBSs were performed for all patients with suspected MPS I

GenotypingMethod: The 14 exons and exon–intron boundaries of the IDUA gene were amplified from DNA samples. Sanger sequencing of each one of the 14 exons was performed. PCR products containing mutations were re-sequenced in both directions. The mutations were further confirmed where possible by restriction analysis (data not shown).

PreviouslyPublished:

Variant: NM_000203.5:c.[208C>T];[1029C>A]

ClinVar: 222997

CAID: CA356984

SupplementalData: n/a