Prevalence and clinical/molecular characteristics of PTEN mutations in Turkish children with autism spectrum disorders and macrocephaly. Issue 8 (16th July 2021)

• Record Type: Journal Article
• Authors: Kaymakcalan, Hande; Kaya, İlyas; Cevher Binici, Nagihan; Nikerel, Emrah; Özbaran, Burcu; Görkem Aksoy, Mehmet; Erbilgin, Seda; Özyurt, Gonca; Jahan, Noor; Çelik, Didem; Yararbaş, Kanay; Yalçınkaya, Leyla; Köse, Sezen; Durak, Sibel; Ercan‐Sencicek, Adife Gulhan
• Is Part Of: Molecular genetics & genomic medicine. Volume 9:Issue 8(2021)
• Page Start: n/a
• Page End: n/a
• Publication Date: 2021-07-16
• Subjects: autism spectrum disorder -- macrocephaly -- mutation -- prevalence -- PTEN; Medical genetics -- Periodicals; Genomics -- Periodicals; 616.042
• DOI: 10.1002/mgg3.1739
• Languages: English
• ISSNs: 2324-9269

Abstract

Abstract: Background: 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. Methods: 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). Conclusion: 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. Abstract : 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 report for the first time a patient with PTEN mutation with hepatosteatosis.