TABLE I.
Sequence Variants Identified in the PTEN Gene in 88 Patients With Autism and Macrocephaly
| Location and nucleotide change | Protein change | Frequency | Head circumference | Inheritance | Siblings | Controls (n =220) |
|---|---|---|---|---|---|---|
| Promoter/5′UTR | ||||||
| −1088C→T | … | 1 | +2.5 SD | NA | NA | 0 |
| −1084C→Ta | … | 1 | +2.2 SD | Maternal | Present in 1 sib with autism and 1 unaffected sib | 2 |
| −1026C→Ab | … | 1 | +3.5 SD | Maternal | Present in 1 unaffected sib | 5 |
| −903G→Ab | … | 2 | +2.6 and +9.6 SDc | ND | ND | ND |
| Exon 1 | ||||||
| c.66C→G | D22E | 1 | +2.1 SD | Paternal | Present in 1 sib with autism | 1 |
| Intron 3 | ||||||
| IVS3-9T→C | … | 1 | +2.2 SD | Maternal | Absent in 1 unaffected sib | 0 |
| Exon 8 | ||||||
| c.976G→A | D326N | 1 | +9.6 SDc | De novo | No siblings | 0 |
NA, DNA not available for analysis; ND, not determined.
a
Described initially as a pathogenic mutation [Zhou et al., 2003] and then as a “variant of unknown significance” [Sarquis et al., 2006].
b
Described elsewhere as a polymorphism [Zhou et al., 2003] or a “variant of unknown significance” [Sarquis et al., 2006].
c
The patient with the de novo c.976G→A mutation in exon 8 and the largest head circumference (+9.6 SD) of all the study group, also had a 903G→A variant in the promoter.