Mitochondrial DNA analysis in clinical laboratory diagnostics

被引:69
作者
Wong, LJC
Boles, RG
机构
[1] Childrens Hosp Los Angeles, Div Med Genet, Los Angeles, CA 90027 USA
[2] Childrens Hosp Los Angeles, Saban Res Inst, Los Angeles, CA 90027 USA
[3] Georgetown Univ, Med Ctr, Inst Mol & Human Genet, Washington, DC 20007 USA
[4] Univ So Calif, Keck Sch Med, Dept Pediat, Los Angeles, CA 90089 USA
关键词
clinical diagnosis; mitochondria; molecular analysis; mtDNA; review; testing;
D O I
10.1016/j.cccn.2004.11.003
中图分类号
R446 [实验室诊断]; R-33 [实验医学、医学实验];
学科分类号
1001 ;
摘要
Mitochondrial disorders are increasingly being diagnosed, especially among patients with multiple, seemingly unrelated, neuromuscular and multi-sytem disorders. The genetics are complex, in particular as the primary mutation can be either on the nuclear or the mitochondrial DNA (mtDNA). mtDNA mutations are often maternally inherited, but can be sporadic or secondary to autosomally inherited mutations in nuclear genes that regulate mtDNA biosynthesis. mtDNA mutations demonstrate extreme variable expressivity in terms of clinical manifestations and severity, even within a family. Disease is often episodic. Several well-defined clinical syndromes associated with specific mutations are described, yet the genotype-phenotype correlation is fair at best and most patients do not fit within any defined syndrome and have rare or novel mutations. In most patients, mutant and wild-type mtDNA coexist ("heteroplasmy"), although homoplasmic mtDNA mutations also are known. "Standard" mtDNA clinical diagnostics usually consists of a PCR-based assay to detect a small number of relatively common point mutations and Southern blotting (or PCR) for large (> 500 bp) rearrangements. In selected cases testing negative, additional analyses can include real-time PCR for mtDNA depletion, and full mtDNA genome screening for the detection of rare and novel point mutations by a variety of methods. Prenatal diagnosis is problematic in most cases. (c) 2004 Elsevier B.V. All rights reserved.
引用
收藏
页码:1 / 20
页数:20
相关论文
共 79 条
  • [31] Macular pattern retinal dystrophy, adult-onset diabetes, and deafness: A family study of A3243G mitochondrial heteroplasmy
    Harrison, TJ
    Boles, RG
    Johnson, DR
    LeBlond, C
    Wong, LJC
    [J]. AMERICAN JOURNAL OF OPHTHALMOLOGY, 1997, 124 (02) : 217 - 221
  • [32] Higashimoto T, 1999, CLIN CHEM, V45, P2005
  • [33] Mitochondrial neurogastrointestinal encephalomyopathy (MNGIE):: A disease of two genomes
    Hirano, M
    Nishigaki, Y
    Martí, R
    [J]. NEUROLOGIST, 2004, 10 (01) : 8 - 17
  • [34] Defects of intergenomic communication:: autosomal disorders that cause multiple deletions and depletion of mitochondrial DNA
    Hirano, M
    Marti, R
    Ferreiro-Barros, C
    Vilà, MR
    Tadesse, S
    Nishigaki, Y
    Nishino, I
    Vu, TH
    [J]. SEMINARS IN CELL & DEVELOPMENTAL BIOLOGY, 2001, 12 (06) : 417 - 427
  • [35] Hirano M, 2003, MOL GENETIC BASIS NE, P197
  • [36] Howell N, 2000, Hum Reprod, V15 Suppl 2, P235
  • [37] Screening for mitochondrial,DNA heteroplasmy in children at risk for mitochondrial disease
    Ito, M
    Le, ST
    Chaudhari, D
    Higashimoto, T
    Maslim, A
    Boles, RG
    [J]. MITOCHONDRION, 2001, 1 (03) : 269 - 278
  • [38] LARSSON NG, 1992, AM J HUM GENET, V50, P360
  • [39] Prenatal exclusion of Leigh syndrome due to T8993C mutation in the mitochondrial DNA
    Leshinsky-Silver, E
    Perach, M
    Basilevsky, E
    Hershkovitz, E
    Yanoov-Sharav, M
    Lerman-Sagie, T
    Lev, D
    [J]. PRENATAL DIAGNOSIS, 2003, 23 (01) : 31 - 33
  • [40] Liang MH, 1998, AM J MED GENET, V77, P395, DOI 10.1002/(SICI)1096-8628(19980605)77:5<395::AID-AJMG8>3.0.CO