Smeets E, Schollen E, Moog U, Matthijs G, Herbergs J, Smeets H, Curfs L, Schrander-Stumpel C, Fryns J P
Department of Human Genetics, University Hospital Gasthuisberg, Leuven, Belgium.
Am J Med Genet A. 2003 Oct 15;122A(3):227-33. doi: 10.1002/ajmg.a.20321.
Rett syndrome (RTT) is a neurodevelopmental disorder which is diagnosed clinically. We report on 30 adolescent and adult females with classical or atypical RTT of whom 24 have a MECP2 mutation. In these 24 females, the clinical manifestations, degree of severity, and disorder profiles are discussed as well as the genotype phenotype correlation. After X-chromosome inactivation (XCI) study in these cases, we found no correlation between skewing and milder phenotype. Three large deletions were found after additional Southern blot analysis in three classical RTT cases. We confirm that early truncating mutations in MECP2 are responsible for a more severe course of the disorder. Three disorder profiles related to the missense mutations R133C and R306C, and to deletions in the C terminal segment are described and are of interest for further clinical study on larger numbers of cases. The R133C genotype has a predominantly autistic presentation while the R306C genotype is associated with a slower disease progression. The phenotype of the "hotspot" deletions in the C terminal segment is predominantly characterized by rapid progressive neurogenic scoliosis. Older women with RTT are underdiagnosed: seven adults were first diagnosed as having RTT between 29 and 60 years of age, and confirmed on finding a MECP2 mutation. Knowledge of the clinical phenotype of RTT at an adult age is important for all involved in the care of these individuals. The involvement of the parent support group is very important in this matter.
瑞特综合征（RTT）是一种通过临床诊断的神经发育障碍疾病。我们报告了30例青少年及成年女性的经典型或非典型瑞特综合征病例，其中24例存在MECP2基因突变。在这24名女性中，我们讨论了其临床表现、严重程度及疾病特征，以及基因型与表型的相关性。对这些病例进行X染色体失活（XCI）研究后，我们发现偏斜与较轻表型之间无相关性。在3例经典型瑞特综合征病例中，通过进一步的Southern印迹分析发现了3个大片段缺失。我们证实，MECP2基因的早期截断突变会导致疾病进程更为严重。描述了与错义突变R133C和R306C以及C末端片段缺失相关的3种疾病特征，这些对于对更多病例进行进一步临床研究具有重要意义。R133C基因型主要表现为自闭症，而R306C基因型与疾病进展较慢有关。C末端片段“热点”缺失的表型主要特征为快速进展性神经源性脊柱侧凸。成年瑞特综合征女性患者存在诊断不足的情况：7名成年人在29至60岁之间首次被诊断为瑞特综合征，经检测发现MECP2基因突变得以确诊。了解成年瑞特综合征的临床表型对于所有参与这些患者护理的人员都很重要。在这件事情上，家长支持小组的参与非常重要。
