Publication date: Jul 16, 2021
Phosphatase and tensin homolog (PTEN) germline mutations are associated with cancer syndromes (PTEN hamartoma tumor syndrome; PHTS) and in pediatric patients with autism spectrum disorder (ASD) and macrocephaly. The exact prevalence of PTEN mutations in patients with ASD and macrocephaly is uncertain; with prevalence rates ranging from 1% to 17%. Most studies are retrospective and contain more adult than pediatric patients, there is a need for more prospective pediatric studies. We recruited 131 patients (108 males, 23 females) with ASD and macrocephaly between the ages of 3 and 18 from five child and adolescent psychiatry clinics in Turkey from July 2018 to December 2019. We defined macrocephaly as occipito-frontal HC size at or greater than 2 standard deviations (SD) above the mean for age and sex on standard growth charts. PTEN gene sequence analysis was performed using a MiSeq next generation sequencing (NGS) platform, (Illumina). PTEN gene sequence analyses identified three pathogenic/likely pathogenic mutations [NM_000314. 6; p. (Pro204Leu), (p. Arg233*) and novel (p. Tyr176Cys*8)] and two variants of uncertain significance (VUS) [NM_000314. 6; p. (Ala79Thr) and c. *10del]. We also report that patient with (p. Tyr176Cys*8) mutation has Grade 1 hepatosteatosis, a phenotype not previously described. This is the first PTEN prevalence study of patients with ASD and macrocephaly in Turkey and South Eastern Europe region with a largest homogenous cohort. The prevalence of PTEN mutations was found 3. 8% (VUS included) or 2. 29% (VUS omitted). We recommend testing for PTEN mutations in all patients with ASD and macrocephaly.
|Autism||Branches of biology|
|Multiple hamartoma syndrome|
|disease||MESH||autism spectrum disorders|
|disease||MESH||PTEN hamartoma tumor syndrome|