Naom I, D'Alessandro M, Sewry C, Ferlini A, Topaloglu H, Helbling-Leclerc A, Guicheney P, Schwartz K, Akcoren Z, Dubowitz V, Muntoni F
Department of Paediatrics and Neonatal Medicine, Hammersmith Hospital, London, UK.
Hum Genet. 1997 Apr;99(4):535-40. doi: 10.1007/s004390050402.
Complete or partial deficiency of the laminin alpha2 chain of merosin has been demonstrated in a proportion of children with classical congenital muscular dystrophy and linkage to the laminin alpha2 chain gene (LAMA2) on chromosome 6q2 has been established. As the laminin alpha2 chain is also expressed in the trophoblast, its detection and linkage analysis are useful tools for prenatal diagnosis. We report our experience of seven prenatal diagnoses in families with partial deficiency or total absence of the laminin alpha2 chain in the muscle of the propositi. In five instances, expression of the laminin alpha2 chain in the trophoblast was normal and linkage data suggested that the fetuses were unaffected. In one family, the immunocytochemical studies of the trophoblast showed the absence of laminin alpha2, suggesting that the fetus was affected. Linkage analysis confirmed that the fetus had inherited the two at-risk haplotypes. In one family with partial laminin alpha2 chain deficiency, the haplotype analysis was hampered by maternal DNA contamination. Immunocytochemical analysis of chorionic villus sampling showed a reduction in laminin alpha2 expression. The pregnancy was presumed to be at high-risk and terminated. However, subsequent analysis of fetal DNA indicated that the fetus was probably heterozygous. Our data suggest that immunocytochemical analysis of the trophoblast can detect abnormalities in affected fetuses and gives normal results in unaffected and carrier fetuses. Nevertheless, we recommend that linkage analysis to the LAMA2 locus is also studied in all cases.
在一部分典型先天性肌营养不良患儿中已证实存在merosin层粘连蛋白α2链的完全或部分缺陷，并且已确定其与6号染色体q2上的层粘连蛋白α2链基因（LAMA2）连锁。由于层粘连蛋白α2链也在滋养层细胞中表达，其检测和连锁分析是产前诊断的有用工具。我们报告了对先证者肌肉中层粘连蛋白α2链部分缺陷或完全缺失的家庭进行七次产前诊断的经验。在五例中，滋养层细胞中层粘连蛋白α2链的表达正常，连锁数据表明胎儿未受影响。在一个家庭中，滋养层细胞的免疫细胞化学研究显示层粘连蛋白α2缺失，提示胎儿受影响。连锁分析证实胎儿继承了两个风险单倍型。在一个层粘连蛋白α2链部分缺陷的家庭中，单倍型分析因母体DNA污染而受阻。绒毛取样的免疫细胞化学分析显示层粘连蛋白α2表达降低。推测该妊娠为高风险并终止。然而，随后对胎儿DNA的分析表明胎儿可能是杂合子。我们的数据表明，滋养层细胞的免疫细胞化学分析可以检测出受影响胎儿的异常情况，而在未受影响和携带致病基因的胎儿中结果正常。尽管如此，我们建议在所有病例中也进行LAMA2基因座的连锁分析。
