Table 2.
Novel genetic variants detected in PCCA and PCCB genes and in silico analysis of pathogenicity.
| Gender | Date of birth | Gene | Nucleotide change | Amino-acid change | Zygosity | Mutation category | PolyPhen-2 | SIFT | Provean | MutationTaster | Age of diagnosis | Clinical Features | Laboratory findings |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Male | 06 Jul 2014 | PCCA | c.111_130del20 | Tyr39Asnfs*5 | Homozygous | frame-shift | N/A | N/A | N/A | N/A | Neonatal period | ID Hypotonia, Recurrent MC, ECEPH and pancreatitis | Recurrent; metabolic acidosis, hyperammonemia, ketonuria. Pancytopenia and increased serum lipase |
| Male | 12 Aug 2007 | PCCA | c.266C > G | Thr89Arg | Homozygous | Missense | Probably damaging | Damaging | Deleterious | Disease causing | ID Hypotonia, Recurrent MC, ECEPH. infrequent pancreatitis, SZ disorder | Recurrent; metabolic acidosis, hyperammonemia, ketonuria. Pancytopenia and increased serum lipase | |
| Male | 01 Oct 2013 | PCCA | c.955C > T | Gln319* | Homozygous | Nonsense | N/A | N/A | N/A | N/A | Mild ID, rare MC | metabolic acidosis | |
| Male | 05 May 2009 | PCCA | c.1375_1391dup + c.1391ins | Homozygous | frame-shift | N/A | N/A | N/A | N/A | Neonatal period | ID Hypotonia, Recurrent MC, ECEPH pancreatitis | Recurrent; metabolic acidosis, hyperammonemia, ketonuria. Pancytopenia and increased serum lipase | |
| Female | 01 Aug 1991 | PCCA | c.2120 T > G | Val707Gly | Homozygous | Missense | Probably damaging | Damaging | Deleterious | Disease causing | ID, Hypotonia, Recurrent MC ECEPH | Recurrent; metabolic acidosis, hyperammonemia, ketonuria. Pancytopenia | |
| Male | 1993 | PCCB | c.90_108delins14 | Ser30Argfs*25 | Homozygous | frame-shift | N/A | N/A | N/A | N/A | ID, Hypotonia, Recurrent MC, ECEPH, Pancreatitis | Recurrent; metabolic acidosis, hyperammonemia, ketonuria. Pancytopenia | |
| Male | 04 Oct 2010 | PCCB | c.518_543del26 | Leu173* | Homozygous | frame-shift | N/A | N/A | N/A | N/A | Neonatal period | ID, Hypotonia, Recurrent MC, ECEPH pancreatitis choreoathetoid movements | Recurrent; metabolic acidosis, hyperammonemia, ketonuria. Pancytopenia |
| Female | 19 Oct 2010 | PCCB | c.629 T > C | Leu210Pro | homozygous | Missense | Probably damaging | Damaging | Deleterious | Disease causing | Neonatal period | ID, Hypotonia, Recurrent MC, ECEPH pancreatitis choreoathetoid movements | Recurrent; metabolic acidosis, hyperammonemia, hypoglycemia ketonuria. Pancytopenia increased serum lipase |
| Male | 22 Oct 2000 | PCCB | c.866G > C/c.990dupT | Arg289Pro Glu331*/ | Compound heterozygous | Missense | Probably damaging | Tolerated | Deleterious | Disease causing | ID, Hypotonia, Recurrent MC less with age, ECEPH infrequent pancreatitis, SZ disorder, | Recurrent; metabolic acidosis, hyperammonemia, ketonuria. Pancytopenia increased serum lipase | |
| Male | 12 Sep 2011 | PCCB | c.1088C > T | Ser363Leu | Homozygous | Missense | Possibly damaging | Damaging | Deleterious | Disease causing | Neonatal period | ID, Hypotonia, Recurrent MC, ECEPH pancreatitis preterm. | Recurrent; metabolic acidosis, hyperammonemia, hypoglycemia ketonuria. Pancytopenia increased serum lipase |
| Female | 15 Apr 2004 | PCCB | c.1163 T > A | Leu388His | Homozygous | Missense | Probably damaging | Damaging | Deleterious | Disease causing | ID, Hypotonia, Recurrent MC ECEPH | Recurrent; metabolic acidosis, hyperammonemia, ketonuria. Pancytopenia |
ID: Intellectual Disability, SZ: Seizure, MC: MC, ECEPH: encephalopathy