Genetikum, Genetic Counseling and Diagnostic, Stuttgart and Neu-Ulm, Germany.
Department of Pediatrics and Neuropediatrics, University Medicine, Göttingen, Germany.
Am J Med Genet A. 2015 Nov;167A(11):2826-9. doi: 10.1002/ajmg.a.37276. Epub 2015 Aug 4.
Menkes disease (MD) is a rare X-linked recessive disorder caused by mutations in the ATP7A gene. This neurodegenerative disorder typically affects males and is characterized by impaired copper distribution and the malfunction of several copper-dependent enzymes. We report clinically discordant female monozygotic twins (MZT) with a heterozygous ATP7A mutation. One twin girl is healthy at the current age of 4 years, whereas the other twin girl developed classical MD, showed disease stabilization under copper histidine treatment but died at the age of 3 years. Presumably, the affected girl developed MD due to skewed X inactivation, although this could not be demonstrated in two tissues (blood, buccal mucosa). This case is a rare example of an affected girl with MD and shows the possibility of a discordant phenotype in MZT girls. As speculated in other X-linked diseases, the process of monozygotic twinning may be associated with skewed X inactivation leading to a discordant phenotype.
Menkes 病（MD）是一种由 ATP7A 基因突变引起的罕见的 X 连锁隐性遗传病。这种神经退行性疾病通常影响男性，其特征是铜分布受损和几种铜依赖性酶的功能障碍。我们报告了临床上不一致的女性同卵双胞胎（MZT），她们携带有杂合性 ATP7A 突变。一个双胞胎女孩目前 4 岁，健康，而另一个双胞胎女孩则发展为经典的 MD，在铜组氨酸治疗下病情稳定，但在 3 岁时死亡。推测受影响的女孩由于 X 染色体失活偏倚而患上 MD，但这在两个组织（血液、口腔黏膜）中都无法证明。该病例是一例罕见的 MD 受累女孩，并显示 MZT 女孩表型不一致的可能性。正如在其他 X 连锁疾病中推测的那样，同卵双胞胎的形成过程可能与 X 染色体失活偏倚有关，导致表型不一致。
