Leber's hereditary optic neuropathy, intellectual disability and epilepsy presenting with variable penetrance associated to the m.3460G >A mutation and a heteroplasmic expansion of the microsatellite in MTRNR1 gene - case report.
Leber's hereditary optic neuropathy, intellectual disability and epilepsy presenting with variable penetrance associated to the m.3460G >A mutation and a heteroplasmic expansion of the microsatellite in MTRNR1 gene - case report.
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DOI：
10.1186/s12881-018-0644-3
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发表时间：
2018-07-27
影响因子：
--
通讯作者：
Petruzzella V
中科院分区：
文献类型：
--
作者：
Bianco A;Bisceglia L;De Caro MF;Galeandro V;De Bonis P;Tullo A;Zoccolella S;Guerriero S;Petruzzella V
与线粒体DNA （mtDNA）突变相关的Leber遗传性视神经病变（LHON）通常仅表现为视神经受累，但在一些患者中可能出现额外的神经系统并发症。这种关联的原因尚不清楚。我们提出一个24岁男性的亚急性，无痛，和迅速进展的双侧视力丧失的历史。我们对先证者及其LHON家族进行了眼科、神经学和神经心理学调查。先证者表现为视神经病变、癫痫、偏头痛和智力残疾；母亲属均无视神经病变，但有中度至重度智力障碍。遗传筛查显示，LHON m.3460G > a突变与线粒体编码12S RNA （MTRNR1）基因中的m.T961delT + C(n)ins存在新的关联，该基因通过母系分支与智力残疾分离。我们还发现，与受影响或对照受试者相比，所有未受影响的人/异质突变携带者的mtDNA含量显著增加。这是首次报道MTRNR1基因突变与LHON原发突变共同分离的病例，这可能是LHON表型并发眼外体征的危险因素。此外，本文报道的数据证实了调节视神经萎缩外显率的关键因素是mtDNA的数量。本文的在线版本（10.1186/s12881-018-0644-3）包含补充材料，仅供授权用户使用。
Leber’s hereditary optic neuropathy (LHON) associated with mutations in mitochondrial DNA (mtDNA) typically manifests only optic nerve involvement but in some patients may develop additional neurological complications. The cause of this association is not clear. We present a case of a 24-year-old male with a history of subacute, painless, and rapidly progressive bilateral vision loss. We performed ophthalmological, neurological and neuropsychological investigations in the proband and his LHON family. The proband showed optic neuropathy, epilepsy, migraine, and intellectual disability; all the maternal relatives did not manifest optic neuropathy but a moderate to severe intellectual disability. Genetic screening revealed a novel association of the LHON m.3460G > A primary mutation with the m.T961delT + C(n)ins within the mitochondrial encoded 12S RNA (MTRNR1) gene which segregates with the intellectual disability through the maternal branch of the family. We also found a significant increase of mtDNA content in all the unaffected homo/heteroplasmic mutation carriers with respect to either affected or control subjects. This is the first case reporting the co-segregation of a mutation in MTRNR1 gene with a LHON primary mutation, which may be a risk factor of the extraocular signs complicating LHON phenotype. In addition, the data herein reported, confirmed that the key factor modulating the penetrance of optic atrophy in the family is the amount of mtDNA. The online version of this article (10.1186/s12881-018-0644-3) contains supplementary material, which is available to authorized users.
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影响因子：
4.3
作者：
Carelli, V;Rugolo, M;Solaini, G
通讯作者：
Solaini, G
影响因子：
5
作者：
Bi, Rui;Zhang, A-Mei;Yao, Yong-Gang
通讯作者：
Yao, Yong-Gang
影响因子：
5.3
作者：
Mengel-From, Jonas;Thinggaard, Mikael;Dalgard, Christine;Kyvik, Kirsten Ohm;Christensen, Kaare;Christiansen, Lene
通讯作者：
Christiansen, Lene
影响因子：
5.3
作者：
Li, ZY;Li, RH;Guan, MX
通讯作者：
Guan, MX
影响因子：
9.9
作者：
La Morgia, C.;Achilli, A.;Carelli, V.
通讯作者：
Carelli, V.