Table 1.
1st mutationb | 2nd mutation | Other mutationsc | |||||||||
---|---|---|---|---|---|---|---|---|---|---|---|
Diagnosisa | Patient ID | Exon | Coding | Protein | Exon | Coding | Protein | Gene | Exon | Coding | Protein |
PEX1 | 674 | Intron 4 | c.473−1G>A | Intron 4 | c.473−1G>A | ||||||
701 | Intron 5 | c.1240+1G>T | 10 | c.1714_1715delCA | p.H572fs | ||||||
719 | 5 | c.547C>T | p.R183X | 23 | c.3732_3736dupCATTA | p.S1246fs | |||||
715 | 10 | c.1769T>G | p.L590R | 10 | c.1769T>G | p.L590R | |||||
627 | 23 | c.3710C>A | p.A1237E | 23 | c.3710C>A | p.A1237E | |||||
707 | 2 | c.270delA | p.Q91fs | 15 | c.2528G>A | p.G843D | |||||
651 | 5 | c.547C>T | p.R183X | 15 | c.2537_2545del9insTCATGGT | p.H846fs | |||||
662 | 5 | c.643_647delACCAA | p.T215fs | 13 | c.2097_2098insT | p.I700fs | |||||
611 | 5 | c.782_783delAA | p.Q261fs | 13 | c.2097_2098insT | p.I700fs | |||||
640 | 5 | c.782_783delAA | p.Q261fs | 15 | c.2528G>A | p.G843D | |||||
649 | 10 | c.1714_1715delCA | p.H572fs | 13 | c.2097_2098insT | p.I700fs | PEX12 | 1 | c.102A>T | p.R34S | |
638 | 10 | c.1714_1715delCA | p.H572fs | 15 | c.2528G>A | p.G843D | |||||
716 | 11 | c.1840delA | p.E615fs | 15 | c.2528G>A | p.G843D | |||||
610 | Intron 11 | c.1900+2T>C | 13 | c.2097_2098insT | p.I700fs | ||||||
601 | 13 | c.2097_2098insT | p.I700fs | Intron 21 | c.3438+2T>C | ||||||
660 | 13 | c.2097_2098insT | p.I700fs | 23 | c.3693_3696delGTCA | p.Q1231fs | |||||
717 | 10 | c.1777G>A | p.G593R | 12 | c.1952_1960dupCAGTGTGGA | p.W653_M654insTVW | |||||
712 | 13 | c.2097_2098insT | p.I700fs | 15 | c.2528G>A | p.G843D | |||||
635 | 14 | c.2392C>G | p.R798G | Intron 18 | c.2926+1G>A | ||||||
672 | 15 | c.2528G>A | p.G843D | 16 | c.2614C>T | p.R872X | PEX6 | 8 | c.1802G>A | p.R601Q | |
606 | 15 | c.2528G>A | p.G843D | 19 | c. 2992C>T | p.R998X | |||||
602 | 13 | c.2097_2098insT | p.I700fs | 13 | c.2097_2098insT | p.I700fs | |||||
608 | 13 | c.2097_2098insT | p.I700fs | 15 | c.2528G>A | p.G843D | |||||
646 | 13 | c.2097_2098insT | p.I700fs | 15 | c.2528G>A | p.G843D | |||||
671 | 13 | c.2097_2098insT | p.I700fs | 18 | c.2916delA | p.G973fs | |||||
702 | 13 | c.2097_2098insT | p.I700fs | 18 | c.2916delA | p.G973fs | |||||
605 | 15 | c.2528G>A | p.G843D | 15 | c.2528G>A | p.G843D | |||||
708 | 15 | c.2528G>A | p.G843D | 18 | c.2916delA | p.G973fs | |||||
616 | 15 | c.2528G>A | p.G843D | 19 | c.3022_3024delCCT | p.P1008del | |||||
| |||||||||||
PEX6 | 710 | 2 | c.914delA | p.D305fs | Intron 9 | c.1962−1G>A | PEX6 | 7 | c.1646C>T | p.A549V | |
609 | 8 | c.1802G>A | p.R601Q | 14 | c.2546A>C | p.N849T | |||||
704d | 8 | c.1802G>A | p.R601Q | 14 | c.2579G>A | p.R860Q | PEX12 | Intron 2 | c.681−2A>C | ||
713 | 8 | c.1802G>A | p.R601Q | 14 | c.2579G>A | p.R860Q | |||||
636 | Intron 1 | c.882+1G>A | 1 | c.821C>T | p.P274L | ||||||
720 | 14 | c.2578C>T | p.R860W | --- | --- | --- | |||||
| |||||||||||
PEX10 | 603 | 1 | c.4delG | p.A2fs | 5 | c.835G>T | p.E279X | ||||
652 | 4 | c.704_705insA | p.L236fs | 4 | c.730C>T | p.R244X | |||||
| |||||||||||
PEX12 | 669 | 2 | c.531_533delACA | p.Q178del | 2 | c.531_533delACA | p.Q178del | ||||
633 | 2 | c.541_542insT | p.Y181fs | 3 | c.730_733dupGCCT | p.L245fs | |||||
607 | 3 | c.887_888delTC | p.L296fs | 3 | c.887_888delTC | p.L296fs | |||||
673 | 3 | c.959C>T | p.S320F | 3 | c.959C>T | p.S320F | |||||
644 | 3 | c.1047_1049delACA | p.Q349del | 3 | c.887delT | p.L296fs | |||||
650 | 3 | c.887_888delTC | p.L296fs | ||||||||
| |||||||||||
PEX26 | 604e | 3 | c.292C>T | p.R98W | 3 | c.292C>T | p.R98W | PEX1 | 18 | c.2843G>A | p.R948Q |
714 | 2 | c.192_216del | p.S64fs | 3 | c.353C>G | p.P118R | |||||
632 | 2 | c.37_38delAG | p.R13fs | Intron 3 | c.667+2T>C | ||||||
634 | 3 | c.292C>T | p.R98W | 4 | c.574C>T | p.R192X | |||||
676 | 3 | c.296G>A | p.W99X | 3 | c.296G>A | p.W99X |
In cases where only one deleterious PEX gene allele was found, we assigned this gene as disease-causing even though it is formally possible that another gene is causative of disease. The GenBank reference numbers for each PEX gene were as follows: PEX1 (NM_000466.2), PEX6 (NM_000287.2), PEX10 (NM_002617.3), PEX12 (NM_000286.1), and PEX26 (AB089678.1).
Novel unreported variants are shown in red. Variants previously not found in these samples, but reported in other datasets are shown in black. Variants previously found in these samples via the PEX Gene Screen are shown in blue. Samples are ordered based on the number of novel deleterious variants uncovered and sub-grouped based on the number of novel alleles discovered in our study. Nucleotide numbering reflects cDNA numbering with +1 corresponding to the A of the ATG translation initiation codon in the reference sequence, according to journal guidelines. The initiation codon is codon 1.
All missense changes occur in amino acids conserved in human, rhesus macaque, mouse, and rat orthologs.
Individual listed has defective PEX6 function via genetic complementation analysis.
Individual listed has defective PEX26 function via genetic complementation analysis.