RT Journal Article
SR Electronic
T1 Identification of pathogenic gene variants in small families with intellectually disabled siblings by exome sequencing
JF Journal of Medical Genetics
JO J Med Genet
FD BMJ Publishing Group Ltd
SP 802
OP 811
DO 10.1136/jmedgenet-2013-101644
VO 50
IS 12
A1 Schuurs-Hoeijmakers, Janneke H M
A1 Vulto-van Silfhout, Anneke T
A1 Vissers, 
Lisenka E L M
A1 van de Vondervoort, Ilse I G M
A1 van Bon, Bregje W M
A1 de Ligt, Joep
A1 Gilissen, Christian
A1 Hehir-Kwa, Jayne Y
A1 Neveling, Kornelia
A1 del Rosario, Marisol
A1 Hira, Gausiya
A1 Reitano, Santina
A1 Vitello, Aurelio
A1 Failla, Pinella
A1 Greco, Donatella
A1 Fichera, Marco
A1 Galesi, Ornella
A1 Kleefstra, Tjitske
A1 Greally, Marie T
A1 Ockeloen, Charlotte W
A1 Willemsen, Marjolein H
A1 Bongers, Ernie M H F
A1 Janssen, Irene M
A1 Pfundt, Rolph
A1 Veltman, 
Joris A
A1 Romano, Corrado
A1 Willemsen, Michèl A
A1 van Bokhoven, Hans
A1 Brunner, Han G
A1 de Vries, Bert B A
A1 de Brouwer, Arjan P M
YR 2013
UL http://jmg.bmj.com/content/50/12/802.abstract
AB Background Intellectual disability (ID) is a common neurodevelopmental disorder affecting 1–3% of the general population. Mutations in more than 10% of all human genes are considered to be involved in this disorder, although the majority of these genes are still unknown. Objectives We investigated 19 small non-consanguineous families with two to five affected siblings in order to identify pathogenic gene variants in known, novel and potential ID candidate genes. Non-consanguineous families have been largely ignored in gene identification studies as small family size precludes prior mapping of the genetic defect. Methods and results Using exome sequencing, we identified pathogenic mutations in three genes, DDHD2, SLC6A8, and SLC9A6, of which the latter two have previously been implicated in X-linked ID phenotypes. In addition, we identified potentially pathogenic mutations in BCORL1 on the X-chromosome and in MCM3AP, PTPRT, SYNE1, and ZNF528 on autosomes. Conclusions We show that potentially pathogenic gene variants can be identified in small, non-consanguineous families with as few as two affected siblings, thus emphasising their value in the identification of syndromic and non-syndromic ID genes.