Whole Xp Deletion in a Girl with Mental Retardation, Epilepsy, and Biochemical Features of OTC Deficiency

被引:3
作者
Joost, K. [1 ,7 ]
Tammur, P. [5 ]
Teek, R. [5 ]
Zilina, O. [2 ,5 ]
Peters, M. [3 ]
Kreile, M. [8 ]
Lace, B. [8 ]
Zordania, R. [7 ]
Talvik, I. [4 ,6 ]
Ounap, K. [4 ,5 ]
机构
[1] Univ Tartu, Ctr Excellence Translat Med, Tartu, Estonia
[2] Univ Tartu, Inst Cell & Mol Biol, Dept Biotechnol, Tartu, Estonia
[3] Univ Tartu, Dept Obstet & Gynecol, Tartu, Estonia
[4] Univ Tartu, Dept Pediat, Tartu, Estonia
[5] Tartu Univ Hosp, Dept Genet, United Labs, Tartu, Estonia
[6] Tartu Univ Hosp, Childrens Clin, Tartu, Estonia
[7] Tallinn Childrens Hosp, Tallinn, Estonia
[8] Children Clin Univ Hosp, Med Genet Clin, Riga, Latvia
关键词
Mental retardation; Ornithine transcarbamylase (OTC) deficiency; Skewed X-inactivation; Turner syndrome; Xp deletion;
D O I
10.1159/000331323
中图分类号
Q3 [遗传学];
学科分类号
071007 ; 090102 ;
摘要
Background: Females with a total or partial deletion of the short arm of the X chromosome have variable features of Turner syndrome, but mental retardation (MR) rarely occurs. The haploinsufficiency of deleted genes that escape X-inactivation may explain the occurrence of MR and autism. Ornithine transcarbamylase (OTC) deficiency is the most common urea cycle disorder and is inherited in an X-linked semidominant trait, and the OTC gene maps to Xp21. Methods: We report on a girl with MR, epilepsy and biochemical changes characteristic of OTC deficiency but no identifiable point mutation in the OTC gene. Standard G-banding cytogenetic analysis, whole genome karyotyping, and X-inactivation studies were performed to determine the genetic etiology of the OTC deficiency in the patient. Results: Cytogenetic analysis and molecular karyotyping using SNP array revealed a deletion of the whole short arm of the X chromosome (Xp22.33-p11.1). Inactivation studies also revealed a completely skewed X-inactivation. Conclusion: Our patient presented with MR, epilepsy, and some evidence of reduced OTC activity, but performed genetic studies gave no explanation for this phenotype. We hope that this case report contributes to the understanding of the underlying genetic factors of the manifestation of X-linked disorders in female patients. Copyright (C) 2011 S. Karger AG, Basel
引用
收藏
页码:311 / 315
页数:5
相关论文
共 16 条
[1]   No evidence that skewing of X chromosome inactivation patterns is transmitted to offspring in humans [J].
Bolduc, Veronique ;
Chagnon, Pierre ;
Provost, Sylvie ;
Dube, Marie-Pierre ;
Belisle, Claude ;
Gingras, Marianne ;
Mollica, Luigina ;
Busque, Lambert .
JOURNAL OF CLINICAL INVESTIGATION, 2008, 118 (01) :333-341
[2]   X-inactivation profile reveals extensive variability in X-linked gene expression in females [J].
Carrel, L ;
Willard, HF .
NATURE, 2005, 434 (7031) :400-404
[3]   Molecular cytogenetic analysis of a familial interstitial deletion Xp22.2-22.3 with a highly variable phenotype in female carriers [J].
Chocholska, S ;
Rossier, E ;
Barbi, G ;
Kehrer-Sawatzki, H .
AMERICAN JOURNAL OF MEDICAL GENETICS PART A, 2006, 140A (06) :604-610
[4]   QuantiSNP: an Objective Bayes Hidden-Markov Model to detect and accurately map copy number variation using SNP genotyping data [J].
Colella, Stefano ;
Yau, Christopher ;
Taylor, Jennifer M. ;
Mirza, Ghazala ;
Butler, Helen ;
Clouston, Penny ;
Bassett, Anne S. ;
Seller, Anneke ;
Holmes, Christopher C. ;
Ragoussis, Jiannis .
NUCLEIC ACIDS RESEARCH, 2007, 35 (06) :2013-2025
[5]   STRUCTURE OF THE HUMAN ORNITHINE TRANSCARBAMYLASE GENE [J].
HATA, A ;
TSUZUKI, T ;
SHIMADA, K ;
TAKIGUCHI, M ;
MORI, M ;
MATSUDA, I .
JOURNAL OF BIOCHEMISTRY, 1988, 103 (02) :302-308
[6]   A study of females with deletions of the short arm of the X chromosome [J].
James, RS ;
Coppin, B ;
Dalton, P ;
Dennis, NR ;
Mitchell, C ;
Sharp, AJ ;
Skuse, DH ;
Thomas, NS ;
Jacobs, PA .
HUMAN GENETICS, 1998, 102 (05) :507-516
[7]   A clinical and molecular study of 26 females with Xp deletions with special emphasis on inherited deletions [J].
Lachlan, KL ;
Youings, S ;
Costa, T ;
Jacobs, PA ;
Thomas, NS .
HUMAN GENETICS, 2006, 118 (05) :640-651
[8]   Girl with partial Turner syndrome and absence epilepsy [J].
Puusepp, Helen ;
Zordania, Riina ;
Paal, Mare ;
Bartsch, Oliver ;
Ounap, Katrin .
PEDIATRIC NEUROLOGY, 2008, 38 (04) :289-292
[9]   Pseudoautosomal deletions encompassing a novel homeobox gene cause growth failure in idiopathic short stature and Turner syndrome [J].
Rao, E ;
Weiss, B ;
Fukami, M ;
Rump, A ;
Niesler, B ;
Mertz, A ;
Muroya, K ;
Binder, G ;
Kirsch, S ;
Winkelmann, M ;
Nordsiek, G ;
Heinrich, U ;
Breuning, MH ;
Ranke, MB ;
Rosenthal, A ;
Ogata, T ;
Rappold, GA .
NATURE GENETICS, 1997, 16 (01) :54-63
[10]  
RICCIUTI FC, 1976, AM J HUM GENET, V28, P332