TABLE 3.

Molecular characteristics of the 42 individuals with Primrose syndrome, compared to the major clinical manifestations

Patient		Variant type	Nucleotide change	Protein change	Macrocephaly	Moderate/severe ID	Autism	Self‐injurious behavior	Distal muscle wasting	Cystic bone lesions	Cataract	Reference
Number	Age
1	0.9 y	Missense	c.626A>G	p.Gly209Arg	−	−	+	+	−	−	−	Current study
2	32 y	Missense	c.1739G>A	p.Cys580Tyr	−	+	+	+	+	n.a.	+	Current study
3	3 y	Missense	c.1749C>G	p.Cys583Trp	−	+	−	−	−	n.a.	n.a.	Cleaver et al 16
4	4.7 y	Missense	c.1760 T>C	p.Phe587Ser	+	+	−	+	−	−	−	Current study
5	3 y	Missense	c.1766C>A	p.Ala589Asp	n.a.	+	+	−	−	−	−	Current study
6	35 y	Missense	c.1768A>C	p.Lys590Gln	+	−	−	−	n.a.	−	−	Posmyjk et al 2011 8
7	31 y	Missense	c.1771C>G	p.Gln591Glu	+	+	+	+	+	+	−	Mathijssen et al 5
8	9 y	Missense	c.1787A>Gc.2002G>A	p.His596Argp.Gly668Arg	+	+	+	−	+	n.a.	−	Casertano et al 12
9	9 y	Missense	c.1794C>G	p.Phe598Leu	+	−	−	−	−	−	−	Current study
10	15.2 y	Missense	c.1800C>G	p.His600Gln	+	+	n.a.	−	−	−	−	Grimsdottir et al 2018 15
11	49 y	Missense	c.1802C>T	p.Thr601Ile	−	−	−	+	+	+	−	Cordeddu et al 10
12	45 y	Missense	c.1805G>C	p.Gly602Ala	+	+	−	−	+	−	−	Cordeddu et al 10
13	2.2 y	Missense	c.1811A>C	p.Lys604Thr	+	n.a.	+	−	−	−	−	Cordeddu et al 10
14	5.3 y	Missense	c.1813C>T	p.Pro605Ser	−	+	n.a.	+	−	n.a.	−	Current study
15	2.6 y	Missense	c.1822C>T	p.Cys608Arg	+	+	−	−	−	n.a.	n.a.	Ferreira et al 17
16	16 y	Missense	c.1832G>A	p.Cys611Tyr	+	+	+	−	−	n.a.	−	Alby et al 13
17	11 y	Missense	c.1837C>T	p.Arg613Cys	+	−	+	−	−	n.a.	−	Alby et al 13
18	5.3 y	Missense	c.1847C>Tc.2221G>A	p.Ser616Phep.Gly741Arg	+	+	+	+	−	n.a.	−	Mattioli et al 11
19		Missense	c.1850 T>C	p.Leu617Ser	+	+	−	+	−	n.a.	n.a.	Cleaver et al 16
20	30 y	Missense	c.1861C>T	p.Leu621Phe	+	n.a.	−	−	+	−	−	Carvalho et al 7
21	3.1 y	Missense	c.1869G>C	p.Lys623Asn	+	+	+	+	−	−	−	Casertano et al 12
22	1.1 y	Missense	c.1871A>C	p.His624Pro	+	n.a.	+	−	−	−	−	Current study
23	2.5 y	Missense	c.1873A>G	p.Met625Val	+	−	n.a.	−	−	n.a.	−	Current study
24	27 y	Missense	c.1873A>G	p.Met625Val	−	+	+	−	+	n.a.	n.a.	Ferreira et al 17
25	49 y	Missense	c.1876G>A	p.Val626Met	n.a.	+	n.a.	n.a.	+	+	n.a.	Battisti et al 4
26	8 y	Missense	c.1879A>G	p.Thr627Ala	−	n.a.	−	−	−	n.a.	−	Cleaver et al 16
27	9.3 y	Missense	c.1898C>T	p.Ala633Val	+	+	+	n.a.	−	n.a.	−	Current study
28	IUD	Missense	c.1906 T>C	p.Cys636Arg	−	n.a.	n.a.	n.a.	n.a.	n.a.	n.a.	Alby et al 13
29	3.4 y	Missense	c.1931C>T	p.Thr644Ile	+	n.a.	n.a.	n.a.	n.a.	n.a.	n.a.	Stellacci et al 14
30	11.3 y	Missense	c.1943C>T	p.Ser648Phe	+	+	−	−	−	n.a.	n.a.	Cleaver et al 16
31	6 y	Missense	c.1945C>T	p.Leu649Phe	−	+	+	n.a.	−	n.a.	−	Yamamoto‐Shimojima et al 25
32	13.4 y	Missense	c.1967A>G	p.His656Arg	+	+	−	+	−	n.a.	n.a.	Cleaver et al 16
33	5.7 y	Insertion/deletion	c.1203del	p.Asp401fsGlufs*26	+	+	+	−	−	n.a.	−	Current study
34	12.4 y	Insertion/deletion	c.1844_1846del	p.615_616del	+	−	+	−	−	−	n.a.	Current study
35	8.5 y	Insertion/deletion	c.1024delC	p.Gln342Serfs*42	+	−	n.a.	−	n.a.	n.a.	n.a.	Stellacci et al 14
36	11 y	Insertion/deletion	c.1568delC	p.Pro523fs	−	−	−	−	−	n.a.	n.a.	Current study
37	13 y	Insertion/deletion	c.1568delC	p.Pro523fs	+	−	+	−	−	n.a.	n.a.	Current study
38	53 y	Insertion/deletion	Del11rs12275693– rs1442927		−	+	−	+	+	+	+	Dalal et al 6
39	31 y	n.a.	n.a.	n.a.	+	+	n.a.	n.a.	+	n.a.	+	Liebrecht et al 9
40	33 y	n.a.	n.a.	n.a.	+	+	n.a.	n.a.	+	+	+	Primrose 1
41	39 y	n.a.	n.a.	n.a.	+	+	n.a.	n.a.	+	+	+	Collacott et al 2
42	43 y	n.a.	n.a.	n.a.	−	n.a.	n.a.	n.a.	+	−	+	Lindor et al 3

Note: + present; − absent; n.a. not available.

Abbreviation: IUD, intrauterine demise.