Summary
The hypothesis of germinal mosaicism in the unaffected mother of two half-sisters affected with Rett syndrome is postulated to explain the unusual recurrence of this genetic disorder affecting only females (1/10000); it might be caused by new X-linked mutations with lethality in male fetuses. The analysis of 34 X-linked restriction fragment length polymorphisms (RFLPs) in these two affected females and in their unaffected mother and half-brother, together with the reconstruction of phase for 15 informative RFLPs in somatic cell hybrids retaining a single X chromosome from each female, has made it possible to exclude some regions of the X chromosome as possible sites of the mutation(s) causing Rett syndrome.
Similar content being viewed by others
References
Brahe C, Serra A (1981) A simple method for fusing human lymphocytes with rodent cell in monolayer by polyethylene glycol. Somat Cell Genet 7:109–115
Comings DE (1986) The genetics of Rett syndrome: the consequences of a disorder where every case is a new mutation. Am J Med Genet [Suppl 1]: 383–388
Davies KE, Mandel JL, Wiessebach J, Fellous M (1987) Report of the committee on the genetic constitution of X and Y chromosomes. Cytogenet Cell Genet 46:1–4
Hagberg B, Aicardi J, Dias K, Ramos O (1983) A progressive syndrome of autism, dementia, ataxia, and loss of purposeful hand use in girls: Rett syndrome. Report of 35 cases. Ann Neurol 14:471–479
Hanefeld F (1985) The clinicla pattern of Rett syndrome. Brain Dev 7:320–325
Hanefeld F, Hanefeld U, Wilichowskie, Schmidtke J (1986) Rettsyndrome — search for genetic markers. Am J Med Genet 24:377–382
Journel H, Melki J, Turleau C, Munnich A, Grouchy J de (1990) Rett phenotype with X/autosome translocation: possible mapping of the gene to the short arm. Am J Med Genet 35:142–147
Kidd KK, Boweock J, Schmidtke J, Track RK, Ricciuti F, Hutchings G, Bale A, et al (1989) Report of the DNA committee and catalogs of cloned and mapped genes and DNA polymorphisms. (10th International Workshop on Human Gene Mapping) Cytogenet Cell Genet 51:622–947
Killian W (1986) On the genetics of Rett syndrome: analysis of family and pedigree data. Am J Med Genet [Suppl 1]: 369–376
Kunkel LM, Smith KD, Boyer SH, Borgaonkar DS, Wachtel SS, Miller OJ, Breg WR, et al (1977) Analysis of human Y-chromosome specific reiterated DNA in chromosome variants. Proc Natl Acad Sci USA 74:1245–1249
Lathrop GM, Lalouel JM (1984) Easy calculation of lod scores and genetic risks on small computers. Am J Hum Genet 36:460–465
Lenz W (1961) Zur Genetik der Incontinentia pigmenti. Ann Paediatr (Basel) 196:149–165
Mandel JL, Willard HF, Nussbaum RL, Davies KE, Romeo G (1988) Report of the committee on the genetic constitution of the X chromosome. Cytogenet Cell Genet 49:107–110
Mandel JL, Willard HF, Nussbaum RL, Romeo G, Puck JM, Davies KE (1989) Report of the committee on the genetic constitution of the X chromosome. (10th International Workshop on Human Gene Mapping) Cytogenet Cell Genet 51:384–437
Migeon BR, Axelman J, Jan de Beur S, Valle D, Mitchell GA, Rosenbaum KN (1989) Selection against lethal alleles in females heterozygous for incontinentia pigmenti. Am J Hum Genet 44:100–106
Romeo G, Archidiacono N, Ferlini A, Rocchi M (1986) Rett syndrome: lack of association with fragile site Xp22 and strategy for genetic mapping of X-linked new mutations. Am J Med Genet [Suppl 1]: 355–359
Roncuzzi L, Fadda S, Mochi M, Prosperi L, Sangiorgi S, Santamaria R, Sbarra D, et al (1985) Mapping of X-linked Decker muscular dystrophy through crossovers identified by DNA polymorphisms and by haplotype characterization in somatic cell hybrids. Am J Hum Genet 37:407–417
Tariverdian G, Kantner G, Vogel F (1987) A monozygotic twin pair with Rett syndrome. Hum Genet 75:88–90
Wahlstrom J, Anvret M (1986) Chromosome finding in the Rett yndrome and a test of two-step mutation theory. Am J Med Genet [Suppl 1]: 361–368
Zoghbi HY, Ledbetter DH, Schultz R, Percy AK, Glaze DG (1990) A de novo X;3 translocation in Rett syndrome. Am J Med Genet 35:148–151
Author information
Authors and Affiliations
Rights and permissions
About this article
Cite this article
Archidiacono, N., Lerone, M., Rocchi, M. et al. Rett syndrome: exclusion mapping following the hypothesis of germinal mosaicism for new X-linked mutations. Hum Genet 86, 604–606 (1991). https://doi.org/10.1007/BF00201549
Received:
Revised:
Issue Date:
DOI: https://doi.org/10.1007/BF00201549