Table 1.
Mutations Identified in CDC45
| Subject | Country of Origin | Allele 1 | Allele 2 | Segregation |
|---|---|---|---|---|
| P1a | UK | c.318C>T, p.Val106= (SE) | c.677A>G, p.Asp226Gly | Het, M, P, (2)b |
| P2 | UK | c.226A>C, p.Asn76His | c.469C>T, p.Arg157Cys | Het, M, P, (1) |
| P3 | USA | c.653+5G>A (SE) | c.1487C>T, p.Pro496Leu | Het, M, P |
| P4 | Bangladesh | c.1A>C, p.Met1? | c.1388C>T, p.Pro463Leu | nps |
| P5 | Bangladesh | c.1270C>T, p.Arg424∗ | c.1388C>T, p.Pro463Leu | Het, M, P |
| P6 | Belgium | c.791C>A, p.Ser264Tyr | c.791C>A, p.Ser264Tyr | Hom, M, P |
| P7-1 | Egypt | c.1660C>T, p.Arg554Trp | c.1660C>T, p.Arg554Trp | Hom, M (P deceased) |
| P7-2 | Egypt | c.1660C>T, p.Arg554Trp | c.1660C>T, p.Arg554Trp | Hom, M, P |
| P8 | Sri Lanka | c.1388C>T, p.Pro463Leu | c.1532delC, p.Pro511Glnfs∗36 | Het, M, P |
| P9-1 | Turkey | c.203A>G, p.Gln68Arg (SE) | c.333C>T, p.Asn111= (SE) | Het, M, P |
| P9-2 | Turkey | c.203A>G, p.Gln68Arg (SE) | c.333C>T, p.Asn111= (SE) | Het, M, P |
| P10c | New Zealand | c.[464A>G; 961C>A], p.[Glu155Gly; Pro321Thr] | c.1440+14C>T (SE) | Het, M, P |
| P11 | Egypt | c.1660C>T, p.Arg554Trp | c.1660C>T, p.Arg554Trp | Hom, M, P |
| P12-1 | the Netherlands | c.(485+1_486−1)_(630+1_631−1)del, p.Ile115_Glu162del | c.893C>T, p.Ala298Val | Het, M, P |
| P12-2 | the Netherlands | c.(485+1_486−1)_(630+1_631−1)del, p.Ile115_Glu162del | c.893C>T, p.Ala298Val | Het, M, P |
Refseq accession: NM_003504.4. Abbreviations are as follows: SE, splicing effect; Het, compound heterozygous in affected individual; nps, no parental samples available; M, mutation identified in mother; P, mutation identified in father; Hom, homozygous in affected individual.
Mutation previously reported28 (note mutation numbering differs in previous publication due to different reference transcript).
Numbers in parentheses indicate number of clinically unaffected siblings shown not to have inherited the compound heterozygous genotype.
Subject P10 segregates two rare missense variants on one allele, in combination with a splice region mutation on the second allele. Based on conservation of CDC45 residues across different species, the p.Pro321Thr variant is more likely to be deleterious as this residue is conserved through to S. cerevisiae (Figure 3).