Autism spectrum disorder associated with low serotonin in CSF and mutations in the SLC29A4 plasma membrane monoamine transporter (PMAT) gene

• Published in: Molecular autism 2014-08, Vol.5 (1), p.43-43, Article 43
• Main Authors: Adamsen, Dea, Ramaekers, Vincent, Ho, Horace Tb, Britschgi, Corinne, Rüfenacht, Véronique, Meili, David, Bobrowski, Elise, Philippe, Paule, Nava, Caroline, Van Maldergem, Lionel, Bruggmann, Rémy, Walitza, Susanne, Wang, Joanne, Grünblatt, Edna, Thöny, Beat
• Format: Article
• Language: English
• Subjects: Human health sciences; Neurologie; Neurology; Pediatrics; Pédiatrie; Sciences de la santé humaine
• ISSN: 2040-2392; 2040-2392
• DOI: 10.1186/2040-2392-5-43

Patients with autism spectrum disorder (ASD) may have low brain serotonin concentrations as reflected by the serotonin end-metabolite 5-hydroxyindolacetic acid (5HIAA) in cerebrospinal fluid (CSF). We sequenced the candidate genes SLC6A4 (SERT), SLC29A4 (PMAT), and GCHFR (GFRP), followed by whole exome analysis. The known heterozygous p.Gly56Ala mutation in the SLC6A4 gene was equally found in the ASD and control populations. Using a genetic candidate gene approach, we identified, in 8 patients of a cohort of 248 with ASD, a high prevalence (3.2%) of three novel heterozygous non-synonymous mutations within the SLC29A4 plasma membrane monoamine transporter (PMAT) gene, c.86A > G (p.Asp29Gly) in two patients, c.412G > A (p.Ala138Thr) in five patients, and c.978 T > G (p.Asp326Glu) in one patient. Genome analysis of unaffected parents confirmed that these PMAT mutations were not de novo but inherited mutations. Upon analyzing over 15,000 normal control chromosomes, only SLC29A4 c.86A > G was found in 23 alleles (0.14%), while neither c.412G > A ( G (