A non-ancestral RPGR missense mutation in families with either recessive or semi-dominant X-linked retinitis pigmentosa

被引:36
作者
Banin, Eyal
Mizrahi-Meissonnier, Liliana
Neis, Ruhama
Silverstein, Shira
Magyar, Istvan
Abeliovich, Dvorah
Roepman, Ronald
Berger, Wolfgang
Rosenberg, Thomas
Sharon, Dror [1 ]
机构
[1] Hebrew Univ Jerusalem, Hadassah Med Ctr, Dept Ophthalmol, Jerusalem, Israel
[2] Hebrew Univ Jerusalem, Hadassah Med Ctr, Dept Human Genet, Jerusalem, Israel
[3] Univ Zurich, Inst Med Genet, Div Med Mol Genet & Gene Diagnost, Zurich, Switzerland
[4] Radboud Univ Nijmegen, Nijmegen Med Ctr, Dept Human Genet, Nijmegen, Netherlands
[5] Natl Eye Clin Visually Impaired, Gordon Norrie Ctr Genet Eye Dis, Hellerup, Denmark
关键词
electroretinography; eye disease; human genetics; mutation analysis; retinitis pigmentosa; X-linked disease;
D O I
10.1002/ajmg.a.31642
中图分类号
Q3 [遗传学];
学科分类号
071007 ; 090102 ;
摘要
Most X-linked diseases show a recessive pattern of inheritance in which female carriers are unaffected. in X-linked retinitis pigmentosa (XLRP), however, both recessive and semi-dominant inheritance patterns have been reported. We identified an Israeli family with semi-dominant XLRP due to a missense mutation (p.G275S) in the RPGR gene. The mutation was previously reported in two Danish families with recessive XLRP. Obligate carriers from the two Danish families had no visual complaints and normal to slightly reduced retinal function, while those from the Israeli family suffered from high myopia, low visual acuity, constricted visual fields, and severely reduced electroretinogram (ERG) amplitudes. The disease-related RPGR haplotype of the Israeli family was found to be different from the one found in the two Danish families, indicating that the mutation arose twice independently on different X-chromosome backgrounds. A series of genetic analyses excluded skewed X-inactivation pattern, chromosomal abnormalities, distorted RPGR expression level, and mutations in candidate genes as the cause for the differences in disease severity of female carriers. To the best of our knowledge, this is the first detailed analysis of an identical mutation causing either a recessive or a semi-dominant X-linked pattern of disease in different families. Our results indicate that an additional gene (or genes), linked to RPGR, modulate disease expression in severely affected carriers. These may be related to the high myopia concomitantly found in affected carriers from the Israeli family. (C) 2007 Wiley-Liss, Inc.
引用
收藏
页码:1150 / 1158
页数:9
相关论文
共 37 条
[1]  
ALLEN RC, 1992, AM J HUM GENET, V51, P1229
[2]   X-linked retinitis pigmentosa:: RPGR mutations in most families with definite X linkage and clustering of mutations in a short sequence stretch of Exon ORF15 [J].
Bader, I ;
Brandau, O ;
Achatz, H ;
Apfelstedt-Sylla, E ;
Hergersberg, M ;
Lorenz, B ;
Wissinger, B ;
Wittwer, B ;
Rudolph, G ;
Meindl, A ;
Meitinger, T .
INVESTIGATIVE OPHTHALMOLOGY & VISUAL SCIENCE, 2003, 44 (04) :1458-1463
[3]   Retinal function abnormalities in patients treated with vigabatrin [J].
Banin, E ;
Shalev, RS ;
Obolensky, A ;
Neis, R ;
Chowers, I ;
Gross-Tsur, V .
ARCHIVES OF OPHTHALMOLOGY, 2003, 121 (06) :811-816
[4]   X chromosome inactivation patterns in Russell-Silver syndrome patients and their mothers [J].
Beever, CL ;
Peñaherrera, MS ;
Langlois, S ;
Robinson, WR .
AMERICAN JOURNAL OF MEDICAL GENETICS PART A, 2003, 123A (03) :231-235
[5]   ELECTRORETINOGRAPHIC TESTING AS AN AID IN DETECTION OF CARRIERS OF X-CHROMOSOME-LINKED RETINITIS PIGMENTOSA [J].
BERSON, EL ;
ROSEN, JB ;
SIMONOFF, EA .
AMERICAN JOURNAL OF OPHTHALMOLOGY, 1979, 87 (04) :460-468
[6]   X-LINKED RETINITIS PIGMENTOSA [J].
BIRD, AC .
BRITISH JOURNAL OF OPHTHALMOLOGY, 1975, 59 (04) :177-199
[7]   A comprehensive mutation analysis of RP2 and RPGR in a north American cohort of families with x-linked retinitis pigmentosa [J].
Breuer, DK ;
Yashar, BM ;
Filippova, E ;
Hiriyanna, S ;
Lyons, RH ;
Mears, AJ ;
Asaye, B ;
Acar, C ;
Vervoort, R ;
Wright, AF ;
Musarella, MA ;
Wheeler, P ;
MacDonald, I ;
Iannaccone, A ;
Birch, D ;
Hoffman, DR ;
Fishman, GA ;
Heckenlively, JR ;
Jacobson, SG ;
Sieving, PA ;
Swaroop, A .
AMERICAN JOURNAL OF HUMAN GENETICS, 2002, 70 (06) :1545-1554
[8]   The causes and consequences of random and non-random X chromosome inactivation in humans [J].
Brown, CJ ;
Robinson, WP .
CLINICAL GENETICS, 2000, 58 (05) :353-363
[9]  
CIDECIYAN AV, 1994, INVEST OPHTH VIS SCI, V35, P3812
[10]   The Tctex1/Tctex2 class of dynein light chains - Dimerization, differential expression, and interaction with the LC8 protein family [J].
DiBella, LM ;
Benashski, SE ;
Tedford, HW ;
Karrison, A ;
Patel-King, RS ;
King, SM .
JOURNAL OF BIOLOGICAL CHEMISTRY, 2001, 276 (17) :14366-14373