Genetic analyses

Blood collection and skin biopsy were performed with patient #2 and his brother (only blood collection) at the Innsbruck Institute of Human Genetics (Innsbruck, Austria) following ethical committee approval by the Institutional Review Board of the Medical University of Innsbruck (Innsbruck, Austria) and informed consent of the patients’ parents. The study complied with the principles set out in the World Medical Association’s of the Declaration of Helsinki. Patient #2 and his only brother were sons of healthy related parents (first cousins once removed) from Turkey. Both patients have moderate intellectual disability. Exomes were enriched in solution with SureSelectHuman All Exon Kit 60 Mb V6 (Agilent, Santa Clara, CA, USA). DNA fragments were sequenced as 100 bp paired-end reads on an IlluminaHiSeq4000 system (Illumina, San Diego,CA, USA). The analysis was carried out considering the inheritance trait and the minor allele frequency (MAF) of <1% in approx. 12,000 exomes in house. The data analysis pipeline has been described in [31]. Sanger sequencing was performed according to standard protocols.