Prevalence and clinical/molecular characteristics of PTEN mutations in Turkish children with autism spectrum disorders and macrocephaly.

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.

Concepts Keywords
Autism Branches of biology
Clinics PTEN
July Autism
Nm_000314 Macrocephaly
Turkey Tensin
Multiple hamartoma syndrome
Autism spectrum


Type Source Name
disease MESH autism spectrum disorders
disease MESH macrocephaly
disease MESH cancer
disease MESH syndromes
disease MESH PTEN hamartoma tumor syndrome
disease MESH growth

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