Homozygous nonsense mutations in KIAA1279 are associated with malformations of the central and enteric nervous systems

被引:113
作者
Brooks, AS
Bertoli-Avella, AM
Burzynski, GM
Breedveld, GJ
Osinga, J
Boven, LG
Hurst, JA
Mancini, GMS
Lequin, MH
de Coo, RF
Matera, I
de Graaff, E
Meijers, C
Willems, PJ
Tibboel, D
Oostra, BA
Hofstra, RMW
机构
[1] Univ Groningen, Dept Med Genet, NL-9713 AW Groningen, Netherlands
[2] Sophia Childrens Univ Hosp, Erasmus MC, Dept Clin Genet, Rotterdam, Netherlands
[3] Sophia Childrens Univ Hosp, Erasmus MC, Dept Radiol, Rotterdam, Netherlands
[4] Sophia Childrens Univ Hosp, Erasmus MC, Dept Pathol, Rotterdam, Netherlands
[5] Sophia Childrens Univ Hosp, Erasmus MC, Dept Child Neurol, Rotterdam, Netherlands
[6] Sophia Childrens Univ Hosp, Erasmus MC, Dept Pediat Surg, Rotterdam, Netherlands
[7] Oxford Radcliffe Hosp, Dept Clin Genet, Oxford, England
[8] Inst G Gaslini, Genet Mol Lab, Genoa, Italy
[9] Gendia, Antwerp, Belgium
关键词
D O I
10.1086/431244
中图分类号
Q3 [遗传学];
学科分类号
071007 ; 090102 ;
摘要
We identified, by homozygosity mapping, a novel locus on 10q21.3- q22.1 for Goldberg- Shprintzen syndrome ( GOSHS) in a consanguineous Moroccan family. Phenotypic features of GOSHS in this inbred family included microcephaly and mental retardation, which are both central nervous system defects, as well as Hirschsprung disease, an enteric nervous system defect. Furthermore, since bilateral generalized polymicogyria was diagnosed in all patients in this family, this feature might also be considered a key feature of the syndrome. We demonstrate that homozygous nonsense mutations in KIAA1279 at 10q22.1, encoding a protein with two tetratrico peptide repeats, underlie this syndromic form of Hirschsprung disease and generalized polymicrogyria, establishing the importance of KIAA1279 in both enteric and central nervous system development.
引用
收藏
页码:120 / 126
页数:7
相关论文
共 23 条
[1]   Large-scale deletions and SMADIP1 truncating mutations in syndromic hirschsprung disease with involvement of midline structures [J].
Amiel, J ;
Espinosa-Parrilla, Y ;
Steffann, J ;
Gosset, P ;
Pelet, A ;
Prieur, M ;
Boute, O ;
Choiset, A ;
Lacombe, D ;
Philip, N ;
Le Merrer, M ;
Tanaka, H ;
Till, M ;
Touraine, R ;
Toutain, A ;
Vekemans, M ;
Munnich, A ;
Lyonnet, S .
AMERICAN JOURNAL OF HUMAN GENETICS, 2001, 69 (06) :1370-1377
[2]   PARABIOTIC TWIN SYNDROME WITH TOPICAL ISOCORTICAL DISRUPTION AND GASTROSCHISIS [J].
BARTH, PG ;
VANDERHARTEN, JJ .
ACTA NEUROPATHOLOGICA, 1985, 67 (3-4) :345-349
[3]  
BARTH PG, 2003, DISORDERS NEURONAL M, P182
[4]  
Brooks AS, 1999, J MED GENET, V36, P485
[5]   Bilateral generalized polymicrogyria (BGP) - A distinct syndrome of cortical malformation [J].
Chang, BS ;
Piao, X ;
Giannini, C ;
Cascino, GD ;
Scheffer, I ;
Woods, CG ;
Topcu, M ;
Tezcan, K ;
Bodell, A ;
Leventer, RJ ;
Barkovich, AJ ;
Grant, PE ;
Walsh, CA .
NEUROLOGY, 2004, 62 (10) :1722-1728
[6]  
Ciardo F, 2001, NEUROPEDIATRICS, V32, P325
[7]   TPR proteins: the versatile helix [J].
D'Andrea, LD ;
Regan, L .
TRENDS IN BIOCHEMICAL SCIENCES, 2003, 28 (12) :655-662
[8]  
Friede RL, 1989, DEV NEUROPATHOLOGY, DOI DOI 10.1007/978-3-642-73697-1
[9]  
GOLDBERG RB, 1981, J CRAN GENET DEV BIO, V1, P185
[10]   UNKNOWN SYNDROME - HIRSCHSPRUNGS-DISEASE, MICROCEPHALY, AND IRIS COLOBOMA - A NEW SYNDROME OF DEFECTIVE NEURONAL MIGRATION [J].
HURST, JA ;
MARKIEWICZ, M ;
KUMAR, D ;
BRETT, EM .
JOURNAL OF MEDICAL GENETICS, 1988, 25 (07) :494-497