Table 2. Overview of mutations detected in one of the five pre-replication genes in individuals with Meier–Gorlin syndrome: biallelic mutations in 35 individuals, monoallelic mutations in three individuals.

Gene	Nucleotide alterations	Amino-acid alterations	Hetero-/homozygous	Putative effect	Number of individuals/families	Individual reference number
ORC1	c.266T>A	p.Phe89Ser	Homozygous	Missense	1/1	1: P3I
	c.314G>A	p.Arg105Gln	Homozygous	Missense	1/1	1: P5
	[c.314G>A]+[c.1482-2A>G]	p.Arg105Gln + intron 9 splice acceptor site	Heterozygous	Missense + splice site	2/2	2: P3, P4I
	[c.314G>A]+[c.1999_2000delGTinsA]	p.Arg105Gln + p.Val667fsX24	Heterozygous	Missense + frameshift	2/1	2: P1, P2
	[c.314G>A]+[c.1996C>T]	p.Arg105Gln + p.Arg666Trp	Heterozygous	Missense	1/1	3: 1983I
	[c.314G>A]+[c.2159G>A]	p.Arg105Gln + p.Arg720Gln	Heterozygous	Missense	1/1	1: P4
	c.380A>G	p.Glu127Gly	Homozygous	Missense	2/1	1: P1, P2
	[c.1721C>T]***	p.Thr57Met	Monoallelic	Missense	1/1	I1 (new individual)II
ORC4	c.521A>G	p.Tyr174Cys	Homozygous	Missense	4/3	2: P6, P7III 3: 1652, 1768, 1769, 1899
	[c.521A>G]+[c.874_875insAACA]	p.Tyr174Cys + p.Ala292fsX19	Heterozygous	Missense + frameshift	2/2	2: P5; 3: 1939
	[c.521A>G]+CNV del	p.Tyr174Cys + del	Heterozygous	Missense + deletion	1/1	3: 1882
ORC6	[c.2T>C]+[c.449+5G>A]	p.Met1? + p.?	Heterozygous	Missense + splice site	4/3	I2, I3, I4, I5 (new individuals)
	[c.257_258delTT]+[c.695A>C]	p.Phe86X + p.Tyr232Ser	Heterozygous	Nonsense + missense	3/1	2: P8, P9, P10
CDT1	[c.196G>A] + [c.351G>C]	p.Ala66Thr + p.Gln117His (exon 2 splicing donor site)	Heterozygous	Missense + splice site	1/1	2: P12
	[c.351G>C]+[c.1385G>A]	p.Gln117His (exon 2 splicing donor site) + p.Arg462Gln	Heterozygous	Splice site + missense	1/1	2: P16
	[c832G>T]+[c.1385G>A]	pGlu278X + p.Arg462Gln	Heterozygous	Nonsense + missense	2/1	I6, I7 (new individuals)
	[c.1081C>T]+[c.1357C>T]	p.Gln361X + p.Arg453Trp	Heterozygous	Nonsense + missense	1/1	2: P17
	[c.1385G>A]+[c1560C>A]	p.Arg462Gln + p.Tyr520X	Heterozygous	Missense + nonsense	4/2	2: P11, P13, P14, P15
	[c.1385G>A]***	p.Arg462Gln	Monoallelic	Missense	2/1	I8, I9III; Bongers et al3
	c.1402G>A	p.Glu468Lys	Homozygous	Missense	1/1	3: 1627
CDC6	c.968C>G	p.Thr323Arg	Homozygous	Missense	1/1	2: P18

1^I=Bicknell et al.¹³

2^I=Bicknell et al.¹⁴

3^I=Guernsey et al.¹⁵

^IIIndividual I1 carries only one mutation in ORC1; Individuals I8 and I9 carry only one mutation in CDT1.

^IIIIndividuals P6 and P7 from the article of Bicknell et al¹⁴ 2011 are the same individuals as 1768 and 1769, respectively, described in the article of Guernsey et al.¹⁵

^***Monoallelic.