Mosaicism for an FMR1 gene deletion in a fragile X female

被引:19
作者
Fan, HX
Booker, JK
McCandless, SE
Shashi, V
Fleming, A
Farber, RA
机构
[1] Univ N Carolina, Dept Pathol & Lab Med, Chapel Hill, NC 27599 USA
[2] Case Western Reserve Univ, Dept Genet, Cleveland, OH 44106 USA
[3] Case Western Reserve Univ, Dept Pediat, Cleveland, OH 44106 USA
[4] Univ Hosp Cleveland, Cleveland, OH 44106 USA
[5] Wake Forest Univ, Sch Med, Dept Pediat, Winston Salem, NC 27109 USA
[6] Univ N Carolina, Dept Genet, Chapel Hill, NC USA
[7] Univ N Carolina, Lineberger Comprehens Canc Ctr, Chapel Hill, NC 27599 USA
关键词
FMR1; gene; deletion; mosaicism; fragile X syndrome; repeat-expansion disorder;
D O I
10.1002/ajmg.a.30807
中图分类号
Q3 [遗传学];
学科分类号
071007 ; 090102 ;
摘要
Most cases of fragile X syndrome result from expansion of CGG repeats in the FMR1 gene; deletions and point mutations of FMR1 are much less common. Mosaicism. for an FMR1 full mutation with a deletion or with a normal allele has been reported in fragile X males. Here we report on a fragile X female who is mosaic for an FMR1 full mutation and an intragenic deletion. The patient is a 4-year-old girl with developmental delay, autistic-like behaviors, and significant speech and language abnormalities. Southern blotting demonstrated the presence of a methylated full mutation, a normal allele in methylated and unmethylated forms, and an additional fragment smaller than the normal methylated allele. This result indicates that the patient is mosaic for a full mutation and a deletion, in the presence of a normal allele. By DNA sequence analysis, we mapped the 5'breakpoint 63/65 bp upstream from the CGG repeat region and the 3'breakpoint 86/88 bp downstream of the CGG repeats within the FMR1 gene. The deletion removed 210 bp, including the entire CGG repeat region. The full mutation was inherited from a premutation in the patient's mother. The deletion, which remained methylated at the Eag I and Nru I sites, was probably derived from the full mutation allele. Mosaicism of this type is rare in females with a fragile X mutation but should be kept in mind in the interpretation of Southern blots. (c) 2005 Wiley-Liss, Inc.
引用
收藏
页码:214 / 217
页数:4
相关论文
共 33 条
[1]  
Allingham-Hawkins SJ, 1999, AM J MED GENET, V83, P322, DOI 10.1002/(SICI)1096-8628(19990402)83:4<322::AID-AJMG17>3.0.CO
[2]  
2-B
[3]   A fragile X case with an amplification/deletion mosaic pattern [J].
Arocena, DG ;
de Diego, Y ;
Oostra, BA ;
Willemsen, R ;
Rodriguez, MM .
HUMAN GENETICS, 2000, 106 (03) :366-369
[4]   Premature ovarian failure and fragile X premutation: a study on 45 women [J].
Bussani, C ;
Papi, L ;
Sestini, R ;
Baldinotti, F ;
Bucciantini, S ;
Bruni, V ;
Scarselli, G .
EUROPEAN JOURNAL OF OBSTETRICS & GYNECOLOGY AND REPRODUCTIVE BIOLOGY, 2004, 112 (02) :189-191
[5]  
DEGRAAFF E, 1995, HUM MOL GENET, V4, P45
[6]  
deGraaff E, 1996, AM J MED GENET, V64, P302, DOI 10.1002/(SICI)1096-8628(19960809)64:2<302::AID-AJMG14>3.0.CO
[7]  
2-J
[8]   VARIATION OF THE CGG REPEAT AT THE FRAGILE-X SITE RESULTS IN GENETIC INSTABILITY - RESOLUTION OF THE SHERMAN PARADOX [J].
FU, YH ;
KUHL, DPA ;
PIZZUTI, A ;
PIERETTI, M ;
SUTCLIFFE, JS ;
RICHARDS, S ;
VERKERK, AJMH ;
HOLDEN, JJA ;
FENWICK, RG ;
WARREN, ST ;
OOSTRA, BA ;
NELSON, DL ;
CASKEY, CT .
CELL, 1991, 67 (06) :1047-1058
[9]  
Grasso M, 1999, AM J MED GENET, V85, P311, DOI 10.1002/(SICI)1096-8628(19990730)85:3<311::AID-AJMG24>3.0.CO
[10]  
2-A