TY - JOUR
T1 - Identification of pathogenic gene variants in small families with intellectually disabled siblings by exome sequencing
AU - Schuurs-Hoeijmakers, Janneke H.M.
AU - Vulto-Van Silfhout, Anneke T.
AU - Vissers, Lisenka E.L.M.
AU - Van De Vondervoort, Ilse I.G.M.
AU - Van Bon, Bregje W.M.
AU - De Ligt, Joep
AU - Gilissen, Christian
AU - Hehir-Kwa, Jayne Y.
AU - Neveling, Kornelia
AU - Del Rosario, Marisol
AU - Hira, Gausiya
AU - Reitano, Santina
AU - Vitello, Aurelio
AU - Failla, Pinella
AU - Greco, Donatella
AU - Fichera, Marco
AU - Galesi, Ornella
AU - Kleefstra, Tjitske
AU - Greally, Marie T.
AU - Ockeloen, Charlotte W.
AU - Willemsen, Marjolein H.
AU - Bongers, Ernie M.H.F.
AU - Janssen, Irene M.
AU - Pfundt, Rolph
AU - Veltman, Joris A.
AU - Romano, Corrado
AU - Willemsen, Michèl A.
AU - Van Bokhoven, Hans
AU - Brunner, Han G.
AU - De Vries, Bert B.A.
AU - De Brouwer, Arjan P.M.
PY - 2013
Y1 - 2013
N2 - 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. Nonconsanguineous 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.
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. Nonconsanguineous 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.
UR - http://www.scopus.com/inward/record.url?scp=84890207463&partnerID=8YFLogxK
U2 - 10.1136/jmedgenet-2013-101644
DO - 10.1136/jmedgenet-2013-101644
M3 - Article
C2 - 24123876
AN - SCOPUS:84890207463
SN - 0022-2593
VL - 50
SP - 802
EP - 811
JO - Journal of Medical Genetics
JF - Journal of Medical Genetics
IS - 12
ER -