Table 1
Case# P4, 4yr onset, Pakistani
CasePresentingHPOs HP:0002151, HP:0001946, HP:0001942, HP:0001987
CasePreviousTesting negative for NAGS and CPS1 genes.
CaseGenotypingMethod sequence analysis of coding exons, including flanking intronic regions of CA5A and CA5B, was performed.
Variant NM_001739.1:c.555+4_555+183del180bp
CAID CA658820661
VariantEvidence intronic splice site
CaseAddInfo consanguineous
In family 2, a male child
Case# F2-2:1, 38wk born, Russian
CasePresentingHPOs HP:0001254, HP:0001824, HP:0001943, HP:0001942, HP:0000952, HP:0002789, HP:0002919
CasePreviousTesting molecular analysis of CPS1 and NAGS did no reveal disease-causing mutations. Metabolic analysis (Table 1)
CaseMethod1 Sanger
CaseGenotypingMethod Sanger of all seven CA5A exons
Variant NM_001739.1(CA5A):c.555G>A (p.Lys185=)
ClinVar 127088
gnomAD 0.0004648 (Other), 0.0001554 (Overall)
VariantEvidence RT-PCR amplifying exons 2-7 of CA5A (in proband and WT) generated different sized products. Sanger of smaller band revealed a deletion in exon 4 (Fig. 3).
CaseAddInfo nonconsanguineous, heterozygous parents
In family 3, a male child
Case# F3-2:5, Male, Pakistan, 13mon diagnosis
CasePresentingHPOs HP:0001987, HP:0001942, HP:0001993, HP:0003128
CasePreviousTesting meningo-encephalitis (cultures were negative). Further metabolic investigations are shown in Table 1.
CaseMethod1 Sanger
CaseGenotypingMethod Sanger of CA5A exons
Variant NM_001739.1(CA5A):c.619-3421_774+502del (p.Asp207_Gln258del)
ClinVar 127089
CaseAddInfo consanguineous, heterozygous parents checked with qtPCR
In family 3, a male child
Case# F3-2:5, Male, Pakistan, 13mon diagnosis
CasePresentingHPOs HP:0001987, HP:0001942, HP:0001993, HP:0003128
CasePreviousTesting meningo-encephalitis (cultures were negative). Further metabolic investigations are shown in Table 1.
CaseMethod1 Sanger
CaseGenotypingMethod Sanger of CA5A exons
Variant NM_001739.1(CA5A):c.619-3421_774+502del (p.Asp207_Gln258del)
ClinVar 127089
CaseAddInfo consanguineous, heterozygous parents checked with qtPCR