Case: Patient 2/ BIODEF 319, female, Caucasian, 10 days

CasePresentingHPOs: HP:0008297, HP:0040210, HP:0040206

HPOtext: Conceived by IVF. HyperPhe detected by neonatal screen, 240umol/L. Plasma Phe levels at 10 days olf was 585 umol.L. BH4 loading test normalized Phe levels. Urine levels showed high neopterin and low biopterin. PCD levels in patient's blood sample were normal. Urine reevalutation showed increased primapterin, again indicating PCD deficiency. cofactor replacement therapy was started, which improved growth trajectories on a normal diet. At 2 years old is still on diet and developing normally.

CaseNOTHPOs:

CasePreviousTesting: n/a

CaseGenotypingMethod: PCR of exons 2-4 of PCBD1 followed by direct sequencing.

Variant 1: NM_000281.3(PCBD1):c.289G>A (p.Glu97Lys)

ClinVar ID 1: 91907

Variant 2: NM_000281.3(PCBD1):c.292C>T (p.Gln98Ter)

ClinVar ID 2: 16799

compound heterozygous

gnomAD variant 1: MAF (Euro-NF)= 2.320E-5 in hets only, no homozygous. http://gnomad.broadinstitute.org/variant/10-72643733-C-T

gnomAD variant 2 n/a

AddCaseInfo: Father carries E97K variant, mother carrier of the Q98X variant, neither are symptomatic.

VariantEvidence: Expression of recombinant protein in bacteria revealed that both the E97K and Q98X variants are present in the insoluble fraction compared to wildtype which is found in the soluble. the little amount retained of each in the soluble fraction showed that they retained activity.

Case: Patient 2/ BIODEF 319, female, Caucasian, 10 days

CasePresentingHPOs: HP:0008297, HP:0040210, HP:0040206

HPOtext: Conceived by IVF. HyperPhe detected by neonatal screen, 240umol/L. Plasma Phe levels at 10 days olf was 585 umol.L. BH4 loading test normalized Phe levels. Urine levels showed high neopterin and low biopterin. PCD levels in patient's blood sample were normal. Urine reevalutation showed increased primapterin, again indicating PCD deficiency. cofactor replacement therapy was started, which improved growth trajectories on a normal diet. At 2 years old is still on diet and developing normally.

CaseNOTHPOs:

CasePreviousTesting: n/a

CaseGenotypingMethod: PCR of exons 2-4 of PCBD1 followed by direct sequencing.

Variant 1: NM_000281.3(PCBD1):c.289G>A (p.Glu97Lys)

ClinVar ID 1: 91907

Variant 2: NM_000281.3(PCBD1):c.292C>T (p.Gln98Ter)

ClinVar ID 2: 16799

compound heterozygous

gnomAD variant 1: MAF (Euro-NF)= 2.320E-5 in hets only, no homozygous. http://gnomad.broadinstitute.org/variant/10-72643733-C-T

gnomAD variant 2 n/a

AddCaseInfo: Father carries E97K variant, mother carrier of the Q98X variant, neither are symptomatic.

VariantEvidence: Expression of recombinant protein in bacteria revealed that both the E97K and Q98X variants are present in the insoluble fraction compared to wildtype which is found in the soluble. the little amount retained of each in the soluble fraction showed that they retained activity.