INTEGRATED STUDY OF 100 PATIENTS WITH XP21 LINKED MUSCULAR-DYSTROPHY USING CLINICAL, GENETIC, IMMUNOCHEMICAL, AND HISTOPATHOLOGICAL DATA .2. CORRELATIONS WITHIN INDIVIDUAL PATIENTS

被引:49
作者
NICHOLSON, LVB
JOHNSON, MA
BUSHBY, KMD
GARDNERMEDWIN, D
CURTIS, A
GINJAAR, IB
DENDUNNEN, JT
WELCH, JL
BUTLER, TJ
BAKKER, E
VANOMMEN, GJB
HARRIS, JB
机构
[1] UNIV NEWCASTLE UPON TYNE, DEPT HUMAN GENET, NEWCASTLE UPON TYNE NE2 4AA, ENGLAND
[2] SYLVIUS LAB, DEPT HUMAN GENET, 2333 AL LEIDEN, NETHERLANDS
[3] UNIV NEWCASTLE UPON TYNE, DEPT MED STAT, NEWCASTLE UPON TYNE NE2 4HH, ENGLAND
[4] NEWCASTLE GEN HOSP, DEPT NEUROPSYCHOL, NEWCASTLE UPON TYNE NE4 6BE, TYNE & WEAR, ENGLAND
基金
英国惠康基金;
关键词
D O I
10.1136/jmg.30.9.737
中图分类号
Q3 [遗传学];
学科分类号
071007 ; 090102 ;
摘要
This report is the second part of a trilogy from a multidisciplinary study which was undertaken to record the relationships between clinical severity and dystrophin gene and protein expression. The aim in part 2 was to correlate the effect of gene deletions on protein expression in individual patients with well defined clinical phenotypes. Among the DMD patients, most of the deletions/duplications disrupted the open reading frame, but three patients had in frame deletions. Some of the intermediate D/BMD patients had mutations which were frameshifting while others were in frame. All of the deletions/duplications in the BMD patients maintained the open reading frame and 25/26 deletions in typical BMD group 5 started with exon 45. The deletion of single exon 44 was the most common mutation in patients from groups 1 to 3. Dystrophin was detected in sections and blots from 58% of the DMD patients with a size that was compatible with synthesis from mRNA in which the reading frame had been restored. Certain deletions were particularly associated with the occurrence of limited dystrophin synthesis in DMD patients. For example, 9/11 DMD patients missing single exons had some detectable dystrophin labelling compared with 10/24 who had deletions affecting more than one exon. All patients missing single exon 44 or 45 had some dystrophin. Deletions starting or finishing with exons 3 or 51 (8/9) cases were usually associated with dystrophin synthesis whereas those starting or finishing with exons 46 or 52 (11/11) were not. Formal IQ assessments (verbal, performance, and full scores) were available for 47 patients. Mean IQ score among the DMD patients was 83 and no clear relationship was found between gene mutations and IQ. The mutations in patients with a particularly severe deficit of verbal IQ were spread throughout the gene.
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页码:737 / 744
页数:8
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