Parental origin of de novo MECP2 mutations in Rett syndrome.
Muriel Girard,Philippe Couvert,Alain Carrié,Marc Tardieu,Jamel Chelly,Cherif Beldjord,Thierry Bienvenu +6 more
TLDR
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.Abstract:
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.read more
Citations
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Perinatal factors and the development of autism: a population study.
Emma J. Glasson,Carol Bower,Beverly Petterson,Nicholas de Klerk,Gervase Chaney,Joachim Hallmayer +5 more
TL;DR: The increased prevalence of obstetric complications among autism cases is most likely due to the underlying genetic factors or an interaction of these factors with the environment.
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Maternal and Paternal Age and Risk of Autism Spectrum Disorders
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Effects of perceived treatment on quality of life and medical outcomes in a double-blind placebo surgery trial.
Cynthia McRae,Eva Cherin,T. Gayle Yamazaki,Gretchen Diem,Alexander H. Vo,Daniel W. Russell,J. Heiner Ellgring,Stanley Fahn,Paul Greene,Sandra Dillon,Hal Winfield,Kimberly B. Bjugstad,Curt R. Freed +12 more
TL;DR: The placebo effect was very strong in this study, demonstrating the value of placebo-controlled surgical trials, and there were numerous differences and changes over time.
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Paternal Age Effect Mutations and Selfish Spermatogonial Selection: Causes and Consequences for Human Disease
Anne Goriely,Andrew O.M. Wilkie +1 more
TL;DR: The data show that PAE mutations, although arising rarely, are positively selected and expand clonally in normal testes through a process akin to oncogenesis, leading to the relative enrichment of mutant sperm over time and explaining the observed paternal age effect associated with these disorders-and in rare cases to the formation of testicular tumors.
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Molecular genetics of Rett syndrome: when DNA methylation goes unrecognized
Thierry Bienvenu,Jamel Chelly +1 more
TL;DR: In vitro assays and microrray studies have delineated the potential molecular mechanisms of MeCP2 function, and have indicated a role in the transcriptional silencing of specific target genes.
References
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Journal ArticleDOI
Rett syndrome is caused by mutations in X-linked MECP2, encoding methyl-CpG-binding protein 2.
Ruthie E. Amir,Ignatia B. Van den Veyver,Mimi Wan,Charles Q. Tran,Uta Francke,Huda Y. Zoghbi +5 more
TL;DR: This study reports the first disease-causing mutations in RTT and points to abnormal epigenetic regulation as the mechanism underlying the pathogenesis of RTT.
Journal ArticleDOI
Analysis of any point mutation in DNA. The amplification refractory mutation system (ARMS)
Clive R. Newton,Alexander Graham,L.E. Heptinstall,S.J. Powell,C Summers,Noor A. Kalsheker,J.C. Smith,A.F. Markham +7 more
TL;DR: The ARMS (Amplification Refractory Mutation System) as discussed by the authors is a system that allows genotyping solely by inspection of reaction mixtures after agarose gel electrophoresis.
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A progressive syndrome of autism, dementia, ataxia, and loss of purposeful hand use in girls: Rett's syndrome: report of 35 cases.
TL;DR: The exclusive involvement of females, correlated with findings in family data analyses, suggests a dominant mutation on one X chromosome that results in affected girls and nonviable male hemizygous conceptuses.
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Detection of Numerous Y Chromosome Biallelic Polymorphisms by Denaturing High-Performance Liquid Chromatography
Peter A. Underhill,Li Jin,Alice A. Lin,S. Qasim Mehdi,Trefor Jenkins,Douglas Vollrath,Ronald W. Davis,Luigi Luca Cavalli-Sforza,Peter J. Oefner +8 more
TL;DR: It is now possible to anticipate the inevitable detailed reconstruction of human Y chromosome genealogy based on several tens to even hundreds of these important polymorphisms.
Journal ArticleDOI
Allele-specific enzymatic amplification of beta-globin genomic DNA for diagnosis of sickle cell anemia.
TL;DR: If ASPCR is able to discriminate all allelic variation (both transition and transversion mutations), this method has the potential to be a powerful approach for genetic disease diagnosis, carrier screening, HLA typing, human gene mapping, forensics, and paternity testing.