Table 1.
Mutations in five genes encoding pre-replication complex proteins in patients with Meier-Gorlin syndrome.
| Family | Patient | Ancestry | Gene | Nucleotide Alterations | Amino Acid Alterations | Exon(s) | Segregation | Parental Consanguinity | Gender | Current Height (SD) | Current OFC (SD) | Microtia | Absent/Small Patellae |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| F1 | P1 | UK | ORC1 | [c.314G>A] + [c.1999_2000delGTinsA] |
R105Q + V667fsX24 | 4; 13 | Het, M, P | No | M | −9.6 | −9.8 | + | + |
| F1 | P2 | UK | ORC1 | [c.314G>A] + [c.1999_2000delGTinsA] |
R105Q + V667fsX24 | 4; 13 | Het, M, P | No | M | NA | NA | + | u |
| F2 | P3 | USA | ORC1 | [c.314G>A] + [c.1482-2A>G] | R105Q + intron 9 splice acceptor site | 4; intron 9 |
Het, M, nps |
No | M | −6.6 | u | + | + |
| F3 | P4 | UK | ORC1 | [c.314G>A] + [c.1482-2A>G] | R105Q + intron 9 splice acceptor site | 4; intron 9 |
Het, M, P | No | F | −6.9 | −4.0 | + | + |
| F4 | P5 | USA | ORC4 | [c.521A>G] + [c.874_875insAACA] | Y174C + A292fsX19 | 8; 11 | Het, M, P | No | F | −6.4 | u | + | + |
| F5 | P6 | USA | ORC4 | c.521A>G | Y174C | 8 | Hom, M, P |
Yes | F | −4.2 | −2.1 | + | − |
| F5 | P7 | USA | ORC4 | c.521A>G | Y174C | 8 | Hom, M, P |
Yes | F | −4.1 | −3.0 | + | − |
| F6 | P8 | TR | ORC6 | [c.257_258delTT] + [c.695A>C] | F86X + Y232S | 3; 7 | Het, M, P | Yes | F | −3.3 | −1.6 | + | + |
| F6 | P9 | TR | ORC6 | [c.257_258delTT] + [c.695A>C] | F86X + Y232S | 3; 7 | Het, M, P | Yes | M | −2.4 | −2.1 | + | + |
| F6 | P10 | TR | ORC6 | [c.257_258delTT] + [c.695A>C] | F86X + Y232S | 3; 7 | Het, M, P | Yes | M | −3.2 | −2.3 | + | + |
| F7 | P11 | NZ | CDT1 | [c.1385G>A] + [c.1560C>A] | R462Q + Y520X | 9; 10 | Het, M, P | No | M | −4.7 | +0.1 | + | + |
| F8 | P12 | UK | CDT1 | [c. 196G>A ] + [c.351G>C] | A66T + Q117H(exon 2 splice donor site) |
1; 2 | Het, M, P | No | F | −5.1 | −5.0 | + | + |
| F9 | P13 | USA | CDT1 | [c.1385G>A] + [c.1560C>A] | R462Q + Y520X | 9; 10 | Het, M, P | Yes | F | −4.7 | −1.3 | + | + |
| F9 | P14 | USA | CDT1 | [c.1385G>A] + [c.1560C>A] | R462Q + Y520X | 9; 10 | Het, M, P | Yes | F | −3.9 | −1.0 | + | + |
| F9 | P15 | USA | CDT1 | [c.1385G>A] + [c.1560C>A] | R462Q + Y520X | 9; 10 | Het, M, P | Yes | M | −1.6 | +1.7 | + | + |
| F10 | P16 | UK | CDT1 | [c.351G>C] + [c.1385G>A] | Q117H(exon 2 splice donor site) + R462Q |
2; 9 | Het, nps | Yes | F | −3.3 | −0.5 | + | + |
| F11 | P17 | SA | CDT1 | [c.1081C>T] + [c.1357C>T] | Q361X + R453W | 7; 9 | Het, M, P | No | F | −0.4 | −2.1 | + | + |
| F12 | P18 | FR | CDC6 | c.968C>G | T323R | 7 | Hom, M, P |
Yes | M | −4.1 | −3.3 | + | + |
Mutations are described numbered from the first nucleotide of the initiation codon in the nucleotide sequence. For each mutation, 380 control chromosomes were screened and found to be negative for the sequence change. Abbreviations: Hom, homozygous in affected individual; Het, compound heterozygous in affected individual, M, mutation identified in mother; P, mutation identified in father; nps, parental sample(s) not available. The protein truncation Y520X in CDT1 is within the last exon and therefore the transcript is not expected to undergo nonsense-medicated mRNA decay. Additionally, in CDT1 the mutation c.351G>C confers a non-conservative amino acid substitution (p.Q117H), however the nucleotide lies within the exon 2 splice donor site and therefore this mutation is expected to result in an inframe deletion of exon 3 from the transcript and resulting protein. TR, Turkey; NZ, New Zealand; FR, France; SA, Saudi Arabia; SD, standard deviation, OFC, occipito-frontal circumference; NA, not available; u, unknown.