Case#: Male, 2-year old

DiseaseAssertion: MPS1-H

FamilyInfo: Not provided

CasePresentingHPOs: Not provided

CaseHPOFreeText: NA

CaseNotHPOs: Not provided

CaseNotHPOFreeText: NA

CaseEnzymeAssay: MPS1-H fibroblasts exhibited no activity of IDUAα (0.01 ± 0.02 nmol/mg/min); iPSC clones were devoid of IDUAα activity

CaseUrineGAGs: Not provided

CaseERT: Don't know

CaseBMT: Don't know

Variant1: NM_000203.5(IDUA):c.1073_1093del (p.His358_Thr364del)

Variant1ClinVarID:557260

Variant1CAID:

Variant2: NM_000203.4(IDUA):c.1205 G>A (p.Trp402Ter)

Variant2ClinVarID:11908

Variant2CAID:

ParentalGenotype: Not provided

PreviouslyPublished: Authors reference [30]: PMID: 31678774 DOI: 10.1016/j.scr.2019.101604

Case: 9, F, 21, Italian

DiseaseAssertion: VWD type 3

FamilyInfo: Consanguinity: no

ParentalGenotype: n/a

CasePresentingHPOs: n/a

CaseHPOFreeText: VWF:Ag (IU/dL): <1, FVIII:C (IU/dL): 3, Bleeding Score: 26

CaseNotHPOs: n/a

CaseNotHPOFreeText: Anti-VWF alloantibodies: no

CasePreviousTesting: n/a

Gene: VWF

Variant:

c.1–30071_220+3445del (p.Met1_Gly74delX8), Exon 1-3

c.3940delG (p.Val1314SerfsX33), Exon 28

Compound Heterozygous

Case: Patient IV-4, Female (mother of proband V-2) DiseaseAssertion: Type 2A VWD, based on history of abnormal bleeding, low plasma VWF:Ag and activity, and lack of plasma HMW VWF multimers. FamilyInfo: Mother of proband V-2; part of 5-affected-member pedigree (Fig. 1). ParentalGenotype(s): Not described (her own parents' genotype status not reported in extracted text — see Figure 1). CasePresentingHPOs: HP:0000421 (Epistaxis), HP:0000132 (Menorrhagia), HP:0012147 (Reduced quantity of VWF; VWF:Ag 21.7 U/dL), HP:0030129 (Impaired VWF:RCo; VWF:Rco 5.0 U/dL), HP:0030132 (Absence of large VWF multimers — plasma), HP:0011871 (Impaired RIPA; 3.0%), HP:0003645 (Prolonged partial thromboplastin time; APTT 46.1 sec) CaseHPOFreeText: Anemia (secondary to menorrhagia; no matching HPO code in the approved list); FVIII:C not tested (N/A); TT 18.1 sec and PT 14.1 sec both within normal range. CaseNOTHPOs: NA CaseNOTHPOFreeText: Platelet VWF multimer status NOT tested for this patient ("Platelet samples were not available from IV-4") — do not assume the "normal platelet multimers" finding reported for the other four affected members applies here. CasePreviousTesting: Targeted confirmation of the familial VWF variant (not described as independent full 52-exon screening for this individual specifically); not genome-wide. GenotypingMethod: Sanger sequencing/allele-specific analysis, same platform as proband (Applied Biosystems 310 DNA analyzer). PreviouslyPublished: NA Gene: VWF Variant: Same novel heterozygous in-frame 6-bp deletion, exon 28, ΔD1529V1530 (VWF A2 domain) HGVS: c.4585_4590del (p.Asp1529_Val1530del) ClinVarID: NA CAID: NA gnomAD: NA

Case: Patient IV-2 (daughter of III-3; first cousin of proband's mother IV-4) DiseaseAssertion: Type 2A VWD, based on low plasma VWF:Ag and activity and lack of plasma HMW VWF multimers. FamilyInfo: Daughter of III-3 (proband's granduncle); first cousin of IV-4 (proband's mother); part of 5-affected-member pedigree (Fig. 1). ParentalGenotype(s): Father (III-3) heterozygous for the variant, affected. Mother's genotype not reported. CasePresentingHPOs: HP:0012147 (Reduced quantity of VWF; VWF:Ag 30.4 U/dL), HP:0030129 (Impaired VWF:RCo; VWF:Rco 8.4 U/dL), HP:0030132 (Absence of large VWF multimers — plasma), HP:0003645 (Prolonged partial thromboplastin time; APTT 45.8 sec) CaseHPOFreeText: Described only generically as having "abnormal bleedings" / "similar clinical symptoms" — no itemized bleeding symptoms given specifically for this individual. FVIII:C 50.0 U/dL — at the exact lower limit of normal (nv 50-150), notably higher than the other affected members. RIPA not tested (N/A). TT 15.6 sec and PT 13.8 sec both within normal range. CaseNOTHPOs: NA CaseNOTHPOFreeText: Platelet-associated VWF multimers normal (HMW multimers present) per the group finding covering this patient. CasePreviousTesting: Targeted confirmation of the familial VWF variant; not genome-wide. GenotypingMethod: Sanger sequencing/allele-specific analysis, same platform as proband. PreviouslyPublished: NA Gene: VWF Variant: Same novel heterozygous in-frame 6-bp deletion, exon 28, ΔD1529V1530 (VWF A2 domain) HGVS: c.4585_4590del (p.Asp1529_Val1530del) ClinVarID: NA CAID: NA gnomAD: NA