Pollitt syndrome patients carry mutation in TTDN1 Sigrid M.A. Swagemakers a , Nicolaas G.J. Jaspers b , Anja Raams b , Daphne Heijsman a , Wim Vermeulen b , Christine Troelstra a , Andreas Kremer a , Stephen E. Lincoln c , Rick Tearle c , Jan H.J. Hoeijmakers b , Peter J. van der Spek a, ⁎ a Department of Bioinformatics, Erasmus University Medical Center, P.O. Box 2040, 3000 CA Rotterdam, The Netherlands b Department of Genetics, Erasmus University Medical Center, P.O. Box 2040, 3000 CA Rotterdam, The Netherlands c Complete Genomics/BGI, Mountain View, CA, USA article info abstract Article history: Received 23 June 2014 Accepted 6 August 2014 Available online xxxx Complete human genome sequencing was used to identify the causative mutation in a family with Pollitt syndrome (MIM #275550), comprising two non-consanguineous parents and their two affected children. The patient's symptoms were reminiscent of the non-photosensitive form of recessively inherited trichothiodystrophy (TTD). A mutation in the TTDN1/C7orf11 gene, a gene that is known to be involved in non- photosensitive TTD, had been excluded by others by Sanger sequencing. Unexpectedly, we did find a homozygous single-base pair deletion in the coding region of this gene, a mutation that is known to cause non- photosensitive TTD. The deleterious variant causing a frame shift at amino acid 93 (C326delA) followed the right mode of inheritance in the family and was independently validated using conventional DNA sequencing. We expect this novel DNA sequencing technology to help redefine phenotypic and genomic variation in patients with (mono) genetic disorders in an unprecedented manner. © 2014 Erasmus University Medical Center. Published by Elsevier B.V. This is an open access article under the CC BY-NC-SA license (http://creativecommons.org/licenses/by-nc-sa/3.0/). Keywords: Pollitt Trichothiodystrophy WGS TTDN1 C7orf11 Pollitt syndrome (MIM #275550) was first described in 1968 (Pollitt et al., 1968) for a brother and sister with mental and physical retardation and trichorrhexis nodosa (pedigree see Fig. 1). Microcephaly and abnormal cerebral cortical cell layering were associated with brittle hair having a 50% reduction in Meta Gene 2 (2014) 616–618 ⁎ Corresponding author. E-mail address: p.vanderspek@erasmusmc.nl (P.J. van der Spek). Contents lists available at ScienceDirect Meta Gene http://dx.doi.org/10.1016/j.mgene.2014.08.001 2214-5400/© 2014 Erasmus University Medical Center. Published by Elsevier B.V. This is an open access article under the CC BY-NC- SA license (http://creativecommons.org/licenses/by-nc-sa/3.0/).