摘要
目的通过对Leber遗传性视神经病变（Leber’s hereditary optic neuropathy，LHON）线粒体DNAND411778G〉A、ND13460G〉A和ND614484T〉C3个原发性突变位点序列分析，阐明LHON患者发病的分子机理。方法PCR扩增35例患者的上述3个原发性突变位点所在的区段，PCR产物直接测序分析。结果35例患者中，6例存在ND411778G〉A突变位点，1例存在ND13460G〉A突变位点，未检出ND614484T〉C突变位点，3个原发性突变位点的检出率为20．0％（7／35）。35例患者均存在ND411719G〉A同义突变，除此突变位点外，23例（65．7％）患者共计筛出21个突变位点，2种突变类型。其中13例患者存在单个突变位点，8例存在2个突变位点，2例存在3个突变位点。21个突变位点中，ND411778G〉A突变频率最高，为28．6％（6／21）；NDI3552T〉A、ND614470T〉C、ND411794T〉C、ND13497C〉T和3644T〉C位点突变频率依次为19．0％（4／21）、19．0％（4／21）、14．3％（3／21）、9．5％（2／21）和9．5％（2／21）。3例存在ND411794T〉C突变位点的患者，2例为异质性突变，1例为同质性突变。结论I。HON患者线粒体DNAND411778G〉A、ND13460G〉A和ND614484T〉C3个原发性致病突变中，以ND411778G〉A为主；继发性突变位点ND13552T〉A或ND13644T〉C单独或协同原发性突变位点ND411778G〉A导致LHON的发生，与单纯携带ND411778G〉A的患者相比视力受损较弱。
Objective To screen for genetic mutations in 35 patients with Leber＇s hereditary optic neuropathy （LHON）. Methods Polymerase chain reaction and DNA sequencing were used to screen for the presence of mitochondrial DNA mutations. Results The total detection rate of top 3 common LHON mutations were 20.0%, which included 6 cases of ND4 11778 G〉A, 1 case of ND1 3460 G〉A. No ND6 14484 T〉C mutation was detected. A ND4 G11719A synonymous mutation was found in all patients. In addition, 21 other mutations were discovered among 23 patients, among which 13 had a single mutation, 8 had a second mutations, and 2 had a third mutation. Among the 21 mutations, ND4 11778 G〉A had a frequency of 28.6%（6/21）. ND1 3552 T〉A, ND6 14470 T〉C, ND4 11794 T〉C, ND1 3497 C〉T and 3644 T〉C respectively had a frequency of 19.0%（4/21）, 19.0%（4/21）, 14.3%（3/21）, 9.5%（2/21） and 9.5%（2/21）. Among the 3 patients who harbored a ND4 11794 T〉C mutation, 2 were heteroplasmic and one was homoplasmic in nature. Conclusion The ND4 11778 G〉A mutation is common in the Top ＂3＂ primary mutations of patients with LHON. Candidate LHON mutation ND1 3552 T〉 A or ND1 3644 T〉 C resulted in LHON pathogenesis as single or synergistic effect. The visual impairment at onset of the disease with candidate mutation were better than the eyes with the ND4 11778 G〉A mutation.
出处
《中华医学遗传学杂志》
CAS
CSCD
北大核心
2012年第5期519-523,共5页
Chinese Journal of Medical Genetics
