Human Genetics

, Volume 69, Issue 4, pp 289–299 | Cite as

Further segregation analysis of the fragile X syndrome with special reference to transmitting males

  • S. L. Sherman
  • P. A. Jacobs
  • N. E. Morton
  • U. Froster-Iskenius
  • P. N. Howard-Peebles
  • K. B. Nielsen
  • M. W. Partington
  • G. R. Sutherland
  • G. Turner
  • M. Watson
Original Investigations

Summary

A new series of 96 pedigrees with the fra(X) syndrome was analysed using complex segregation analysis with pointers, defining affection as any degree of mental impairment. These families were found to exhibit the same segregation pattern as the first series of 110 pedigrees (Sherman et al. 1984). The best estimate for penetrance of mental impairment in males was 79% and in females was 35% for the combined data. Again, there was little evidence for sporadic cases among affected males.

Many more intellectually normal transmitting males have been observed since the existence of such males and the concomitant need to investigate the paternal side of pedigrees was recognized. On further investigation of all 206 pedigrees from the old and new data sets, the sibships of nonexpressing males appeared to be different from those of expressing males. Our analysis, using mental impairment as the phenotype, suggested that obligate carrier mothers and daughters of intellectually normal transmitting males are rarely, if ever, mentally impaired and that the sibs of transmitting males are much less likely to be retarded than the sibs of mentally impaired males. Though mothers and daughters of transmitting males are similar in phenotype, the expression of the gene in their offspring appears to be different: the penetrance of mental impairment is higher in offspring of intellectually normal daughters of transmitting males than in offspring of intellectually normal mothers of transmitting males. The implications of these observations for genetic counseling and for genetic models of the fra(X) syndrome are discussed.

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Appendix I. Information on 110 pedigrees analysed in Sherman et al. 1984 Table 1. References for 51 pedigrees taken from the literature

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Appendix I Table 2. Canadian (JC) and Hawaiian (JH) pedigrees

  1. Dunn HG, Renpenning H, Gerrard JW, Miller JR, Tabata T, Federoff S (1962) Mental retardation as a sex-linked defect. Am J Ment Defic 67:827–848Google Scholar
  2. Jacobs PA, Glover TW, Mayer M, Fox P, Gerrard JW, Dunn HG, Herbst DS (1980) X-linked mental retardation: a study of 7 families. Am J Med Genet 7:471–489Google Scholar
  3. Rhoads FA, Oglesby AC, Mayer M, Jacobs PA (1982) Marker X syndrome in an Oriental family with probably transmission by a normal male. Am J Med Genet 12:205–217Google Scholar
  4. Proops R, Mayer M, Jacobs PA (1983) A study of mental retardation in children in the Island of Hawaii. Clin Genet 23:81–96Google Scholar
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Appendix I Table 3. Australian pedigrees (GT)

  1. Turner G, Brookwell R, Daniel A, Selikowitz M, Zilibowitz M (1980) Heterozygous expression of X-linked mental retardation and X-chromosome marker fra(X)(q27). N Engl J Med 303:662–664Google Scholar
  2. Fishburn J, Turner G, Daniel A, Brookwell R (1983) The diagnosis and frequency of X-linked conditions in a cohort of moderately retarded males with affected brothers. Am J Med Genet 14:713–724Google Scholar
  3. Turner G, Eastman C, Casey J, McLeay A, Procofis P, Turner B (1975) X-linked mental retardation associated with macro-orchidism. J Med Genet 12:367–371Google Scholar

Appendix II. Information on 96 pedigrees analysed in present communication. Table 1. Pedigrees of U. Froster-Iskenius (UF)

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Appendix II Table 2. Pedigress of P. Howard-Peebles (HP)

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Appendix II Table 3. Pedigrees of K. B. Nielsen (BN)

  1. Nielsen KB, Tommerup N, Poulsen H, Mikkelsen M (1981) X-linked mental retardation with fragile X. A pedigree showing transmission by apparently unaffected males and partial expression in female carriers. Hum Genet 59:23–25Google Scholar

Appendix II Table 4. Pedigrees of M. W. Partington (MP)

  1. Uchida IA, Freeman VCP, Jamro H, Partington MW, Soltan HC (1983) Additional evidence for fragile X activity in heterozygous carriers. Am J Hum Genet 35:861–868Google Scholar

Copyright information

© Springer-Verlag 1985

Authors and Affiliations

  • S. L. Sherman
    • 1
  • P. A. Jacobs
    • 2
  • N. E. Morton
    • 1
  • U. Froster-Iskenius
    • 3
  • P. N. Howard-Peebles
    • 4
  • K. B. Nielsen
    • 5
  • M. W. Partington
    • 6
  • G. R. Sutherland
    • 7
  • G. Turner
    • 8
  • M. Watson
    • 9
  1. 1.Population Genetics LaboratoryUniversity of HawaiiHonoluluUSA
  2. 2.Department of Anatomy and Reproductive Biology, John A Burns School of MedicineUniversity of HawaiiHonoluluUSA
  3. 3.Institut für Humangenetik, LübeckLübeck
  4. 4.Department of PathologyUniversity of Texas Health Science Center at DallasDallasUSA
  5. 5.Department of Medical GeneticsThe John F. Kennedy InstituteGlostrupDenmark
  6. 6.Department of PaediatricsQueens UniversityKingstonCanada
  7. 7.Cytogenetics Unit, Department of HistopathologyAdelaide Children's HospitalNorth AdelaideAustralia
  8. 8.The Prince of Wales Children's HospitalRandwickAustralia
  9. 9.Department of Human GeneticsYale University, School of MedicineNew HavenUSA

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