title: Pollitt syndrome patients carry mutation in TTDN1.
abstract: 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.
authors.affiliation: Department of Bioinformatics, Erasmus University Medical Center, P.O. Box 2040, 3000 CA Rotterdam, The Netherlands.
authors.forename: Sigrid M A
authors.initials: SM
authors.lastname: Swagemakers
authors.affiliation: Department of Genetics, Erasmus University Medical Center, P.O. Box 2040, 3000 CA Rotterdam, The Netherlands.
authors.forename: Nicolaas G J
authors.initials: NG
authors.lastname: Jaspers
authors.affiliation: Department of Genetics, Erasmus University Medical Center, P.O. Box 2040, 3000 CA Rotterdam, The Netherlands.
authors.forename: Anja
authors.initials: A
authors.lastname: Raams
authors.affiliation: Department of Bioinformatics, Erasmus University Medical Center, P.O. Box 2040, 3000 CA Rotterdam, The Netherlands.
authors.forename: Daphne
authors.initials: D
authors.lastname: Heijsman
authors.affiliation: Department of Genetics, Erasmus University Medical Center, P.O. Box 2040, 3000 CA Rotterdam, The Netherlands.
authors.forename: Wim
authors.initials: W
authors.lastname: Vermeulen
authors.affiliation: Department of Bioinformatics, Erasmus University Medical Center, P.O. Box 2040, 3000 CA Rotterdam, The Netherlands.
authors.forename: Christine
authors.initials: C
authors.lastname: Troelstra
authors.affiliation: Department of Bioinformatics, Erasmus University Medical Center, P.O. Box 2040, 3000 CA Rotterdam, The Netherlands.
authors.forename: Andreas
authors.initials: A
authors.lastname: Kremer
authors.affiliation: Complete Genomics/BGI, Mountain View, CA, USA.
authors.forename: Stephen E
authors.initials: SE
authors.lastname: Lincoln
authors.affiliation: Complete Genomics/BGI, Mountain View, CA, USA.
authors.forename: Rick
authors.initials: R
authors.lastname: Tearle
authors.affiliation: Department of Genetics, Erasmus University Medical Center, P.O. Box 2040, 3000 CA Rotterdam, The Netherlands.
authors.forename: Jan H J
authors.initials: JH
authors.lastname: Hoeijmakers
authors.affiliation: Department of Bioinformatics, Erasmus University Medical Center, P.O. Box 2040, 3000 CA Rotterdam, The Netherlands.
authors.forename: Peter J
authors.initials: PJ
authors.lastname: van der Spek
keywords: C7orf11; Pollitt; TTDN1; Trichothiodystrophy; WGS