PT  - JOURNAL ARTICLE
AU  - M G Butler
AU  - M J Dasouki
AU  - X-P Zhou
AU  - Z Talebizadeh
AU  - M Brown
AU  - T N Takahashi
AU  - J H Miles
AU  - C H Wang
AU  - R Stratton
AU  - R Pilarski
AU  - C Eng
TI  - Subset of individuals with autism spectrum disorders and extreme macrocephaly associated with germline <em>PTEN</em> tumour suppressor gene mutations
AID  - 10.1136/jmg.2004.024646
DP  - 2005 Apr 01
TA  - Journal of Medical Genetics
PG  - 318--321
VI  - 42
IP  - 4
4099  - http://jmg.bmj.com/content/42/4/318.short
4100  - http://jmg.bmj.com/content/42/4/318.full
SO  - J Med Genet2005 Apr 01; 42
AB  - The genetic aetiology of autism remains elusive. Occasionally, individuals with Cowden syndrome (a cancer syndrome) and other related hamartoma disorders such as Bannayan-Riley-Ruvalcaba syndrome, Proteus syndrome, and Proteus-like conditions, are characterised by germline PTEN mutations, and may have neurobehavioural features resembling autism as well as overgrowth and macrocephaly. Therefore, we undertook PTEN gene mutation analysis in 18 subjects mainly prospectively ascertained with autism spectrum disorder and macrocephaly. Of these 18 autistic subjects (13 males and five females; ages 3.1–18.4 years) with a head circumference range from 2.5 to 8.0 standard deviations above the mean, three males (17%) carried germline PTEN mutations. These three probands had previously undescribed PTEN mutations: H93R (exon 4), D252G (exon 7), and F241S (exon 7). They had the larger head circumference measurements amongst all our study subjects. The three residues altered in our patients were highly evolutionarily conserved. We suggest that PTEN gene testing be considered for patients with autistic behaviour and extreme macrocephaly. The gene findings may impact on recurrence risks as well as medical management for the patient.