Novel mutations in the LAMB3 gene shared by two Japanese unrelated families with Herlitz junctional epidermolysis bullosa, and their application for prenatal testing.
Novel mutations in the LAMB3 gene shared by two Japanese unrelated families with Herlitz junctional epidermolysis bullosa, and their application for prenatal testing.
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两个日本无亲缘关系的 Herlitz 交界性大疱性表皮松解症家族共有的 LAMB3 基因的新突变及其在产前检测中的应用。
DOI：
10.1046/j.1523-1747.1998.00105.x
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发表时间：
1998
期刊：
影响因子：
--
通讯作者：
Nishikawa,T
中科院分区：
文献类型：
--
作者：
Takizawa,Y;Shimizu,H;Pulkkinen,L;Hiraoka,Y;McGrath,JA;Suzumori,K;Aiso,S;Uitto,J;Nishikawa,T
LAMB3基因编码层粘连蛋白5的β3链，是常染色体隐性遗传性水疱性皮肤病（交界性大疱性表皮病）突变的候选基因。在这项研究中，我们进行了遗传分析，在两个不相关的日本家庭与赫利茨交界处大疱性表皮，并确定了两个新的无义突变的LAMB3基因。其中一个为Q166X（CAG → TAG），存在于家系1的母系等位基因和家系2的父系等位基因中。另一个突变W610X（TGG → TGA）则分别出现在家系1的父亲等位基因和家系2的母亲等位基因中。因此，这两个家庭的先证者是这些无义突变的复合杂合子。单倍型分析与基因内LAMB3多态性表明，这两个突变独立出现在这两个家庭。两种突变均产生提前翻译终止密码子，预测截短的β3链导致表皮基底膜区层粘连蛋白5表达缺失。基于这些结果，基于DNA的产前诊断进行了绒毛取样，随后在两个家庭的怀孕。发现两个胎儿都是W610X突变和正常LAMB3等位基因的杂合子携带者，表明它们的表型不受影响。这些研究结果扩大了连接性大疱性表皮病的LAMB3突变库，并强调了层粘连蛋白5基因的两个等位基因中的提前终止密码子导致Herlitz连接性大疱性表皮病的概念。
The LAMB3 gene encoding the β3 chain of laminin 5 is a candidate gene for mutations in the autosomal recessive blistering skin disorder, junctional epidermolysis bullosa. In this study, we performed genetic analyses in two unrelated Japanese families with Herlitz junctional epidermolysis bullosa and identified two novel nonsense mutations in the LAMB3 gene. One of them, Q166X (CAG → TAG), was found in the maternal allele of family 1 and the paternal allele of family 2. Conversely, the other mutation, W610X (TGG → TGA), was found in the paternal allele of family 1 and the maternal allele of family 2. Thus, probands of both families were compound heterozygotes for these nonsense mutations. Haplotype analyses with intragenic LAMB3 polymorphisms suggested that both mutations had arisen independently in these two families. Both mutations create a premature translation termination codon predicting truncated β3 chains that lead to absent expression of laminin 5 in the epidermal basement membrane zone. Based on these results, DNA-based prenatal diagnosis was performed by chorionic villus sampling for subsequent pregnancies in both families. Both fetuses were found to be heterozygous carriers of the W610X mutation together with a normal LAMB3 allele, indicating that they were phenotypically unaffected. These findings expand the repertoire of LAMB3 mutations in junctional epidermolysis bullosa, and emphasize the notion that premature termination codons in both alleles of the laminin 5 genes result in Herlitz junctional epidermolysis bullosa.
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赫利茨交界性大疱性表皮松解症患者 LAMC2 基因纯合外显子跳跃突变的鉴定。
DOI：
10.1111/1523-1747.ep12666027
发表时间：
1995
期刊：
The Journal of investigative dermatology
影响因子：
--
作者：
Vailly,J;Pulkkinen,L;Christiano,AM;Tryggvason,K;Uitto,J;Ortonne,JP;Meneguzzi,G
通讯作者：
Meneguzzi,G
大疱性表皮松解症的产前诊断
DOI：
10.1016/s0140-6736(80)91404-x
发表时间：
1980
期刊：
The Lancet
影响因子：
--
作者：
C. Rodeck;R. Eady;C. Gosden
通讯作者：
C. Gosden
影响因子：
3.5
作者：
KIVIRIKKO, S;MCGRATH, JA;CHRISTIANO, AM
通讯作者：
CHRISTIANO, AM
赫利兹交界性大疱性表皮松解症中新型 LAMC2 突变的检测
影响因子：
5.7
作者：
L. Pulkkinen;J. McGrath;T. Airenne;H. Haakana;K. Tryggvason;S. Kivirikko;G. Meneguzzi;J. Ortonne;A. Christiano;J. Uitto
通讯作者：
J. Uitto
使用新型抗体探针快速产前诊断和排除大疱性表皮松解症。
影响因子：
6.5
作者：
Adrian;H. M. Hcagcrty;A. R. Kennedy;David;Gunner;A. Robin;Eady;P. F.R.C.;Dcparrn
通讯作者：
Dcparrn