Parental origin of de novo MECP2 mutations in Rett syndrome

被引:0
作者
Muriel Girard
Philippe Couvert
Alain Carrié
Marc Tardieu
Jamel Chelly
Cherif Beldjord
Thierry Bienvenu
机构
[1] Laboratoire de Génétique et Physiopathologie des retards mentaux-ICGM,Département de Pédiatrie
[2] Faculté de Médecine Cochin,undefined
[3] Service de Neurologie,undefined
[4] CHU Bicêtre,undefined
[5] 78 rue du Général Leclerc,undefined
来源
European Journal of Human Genetics | 2001年 / 9卷
关键词
gene; Rett syndrome; parental origin;
D O I
暂无
中图分类号
学科分类号
摘要
Rett syndrome (RTT) is a neurodevelopmental disorder occurring almost exclusively in females as sporadic cases. Recently, DNA mutations in the MECP2 gene have been detected in approximately 70% of patients with RTT. To explain the sex-limited expression of RTT, it has been suggested that de novo X-linked mutations occur exclusively in male germ cells resulting therefore only in affected daughters. To test this hypothesis, we have analysed 19 families with RTT syndrome due to MECP2 molecular defects. In seven informative families we have found by DHPLC a nucleotide variant which could be used to differentiate between the maternal and the paternal allele. In each subject investigated from these families, we have amplified specifically each allele and sequenced allele-specific PCR products to identify the allele bearing the mutation as well as the parental origin of each X chromosome. This approach allowed us to determine the parental origin of de novo mutations in all informative families. In five cases, the de novo MECP2 mutations have a paternal origin and in the two other cases a maternal origin. In all transitions at CpG, the de novo mutation observed was of paternal origin. The high frequency of male germ-line transmission of the mutation (71% of RTT informative cases) is consistent with a predominant occurrence of the disease in females.
引用
收藏
页码:231 / 236
页数:5
相关论文
共 77 条
[1]  
Hagberg B(1983)A progressive syndrome of autism, dementia, ataxia and loss of purposeful hand use in girls: Rett's syndrome: report of 35 cases. Ann Neurol 14 471-479
[2]  
Aicardi J(1999)Rett syndrome is caused by mutations in X-linked MECP2, encoding methyl-CpG-binding protein 2. Nature Genet 23 185-188
[3]  
Dias K(2000)Methyl-CpG-binding protein 2 mutations in Rett Syndrome. Curr Opin Genet Dev 10 275-279
[4]  
Ramos O(2000)MECP2 mutations account for most cases of typical forms of Rett syndrome. Hum Mol Genet 9 1377-1384
[5]  
Amir RE(2000)Influence of mutation type and X chromosome inactivation on Rett syndrome phenotypes. Ann Neurol 47 670-679
[6]  
Van der Veyver IB(1999)Rett syndrome and beyond: Recurrent spontaneous and familial MECP2 mutations at CpG hotspots. Am J Hum Genet 65 1520-1529
[7]  
Wan M(1996)High male:female ratio of germ-line line mutations: an alternative explanation for postulated gestational lethality in males in X-linked dominant disorders. Am J Hum Genet 58 1364-1368
[8]  
Tran CQ(1989)Allele-specific enzymatic amplification of β-globin genomic DNA for diagnosis of sickle cell anemia. Proc Natl Acad Sci 86 2757-2760
[9]  
Francke U(1989)Analysis of any point mutation in DNA. The amplification refractory system (ARMS). Nucl Acids Res 7 2503-2516
[10]  
Zoghbi HY(1999)A new member of the IL-1 receptor family highly expressed in the hippocampus and involved in X-linked mental retardation. Nat Genet 23 25-31