Fragile (X) X-linked Mental Retardation. II. Frequency and Replication Pattern of Fragile (X)(q28) in Heterozygotes

Overview

Journal Am J Hum Genet

Publisher Cell Press

Specialty Genetics

Date 1984 May 1

PMID 6731439

Citations 8

Authors

J H Knoll

A E Chudley

J W Gerrard

Affiliations

Soon will be listed here.

Abstract

The frequency of cytologic expression and the replication pattern of the fragile (X) [fra(X)] were investigated in 28 fra(X) heterozygotes, of which 25 agreed to psychological assessment. One-third of the heterozygotes in this study are mentally retarded. The intellectually impaired carriers had a higher frequency of fra(X) and a higher proportion of early-replicating fra(X) than the normally intelligent carriers. The early-replicating fra(X) accounted for 39% of the variability in IQ and the late-replicating fra(X) for 12%. Age had a minimal inverse effect on fra(X) expression and replication pattern. Thus, it appears that mental retardation in females heterozygous for the fra(X) may largely be a function of the proportion of cells with an early-replicating, active X chromosome possessing the fragile site.

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References

NIELSEN K, Tommerup N, POULSEN H, Mikkelsen M . X-linked mental retardation with fragile X. A pedigree showing transmission by apparently unaffected males and partial expression in female carriers. Hum Genet. 1981; 59(1):23-5. DOI: 10.1007/BF00278849. View

Snyder R, Robinson A . Recessive sex-linked mental retardation in the absence of other recognizable abnormalities. Report of a family. Clin Pediatr (Phila). 1969; 8(11):669-74. DOI: 10.1177/000992286900801114. View

Willard H, LATT S . Analysis of deoxyribonucleic acid replication in human X chromosomes by fluorescence microscopy. Am J Hum Genet. 1976; 28(3):213-27. PMC: 1685019. View

RUVALCABA R, Myhre S, ROOSEN-RUNGE E, Beckwith J . X-linked mental deficiency megalotestes syndrome. JAMA. 1977; 238(15):1646-50. View

Deroover J, Fryns J, Parloir C, Van Den Berghe H . X-linked recessively inherited non-specific mental retardation. Report of a large family. Ann Genet. 1977; 20(4):263-8. View

Turner G, Daniel A, Frost M . X-linked mental retardation, macro-orchidism, and the Xq27 fragile site. J Pediatr. 1980; 96(5):837-41. DOI: 10.1016/s0022-3476(80)80552-x. View

Turner G, Brookwell R, Daniel A, Selikowitz M, Zilibowitz M . Heterozygous expression of X-linked mental retardation and X-chromosome marker fra(X)(q27). N Engl J Med. 1980; 303(12):662-4. DOI: 10.1056/NEJM198009183031202. View

Jennings M, Hall J, Hoehn H . Significance of phenotypic and chromosomal abnormalities in X-linked mental retardation (Martin-Bell or Renpenning syndrome). Am J Med Genet. 1980; 7(4):417-32. DOI: 10.1002/ajmg.1320070404. View

Jacobs P, Glover T, Mayer M, Fox P, Gerrard J, Dunn H . X-linked mental retardation: a study of 7 families. Am J Med Genet. 1980; 7(4):471-89. DOI: 10.1002/ajmg.1320070408. View

10.

. Fragile sites in human chromosomes II: demonstration of the fragile site Xq27 in carriers of X-linked mental retardation. Am J Med Genet. 1980; 7(4):497-501. DOI: 10.1002/ajmg.1320070410. View

11.

Proops R, Webb T . The 'fragile' X chromosome in the Martin-Bell-Renpenning syndrome and in males with other forms of familial mental retardation. J Med Genet. 1981; 18(5):366-73. PMC: 1048759. DOI: 10.1136/jmg.18.5.366. View

12.

Webb G, Halliday J, PITT D, JUDGE C, Leversha M . Fragile (X)(q27) sites in a pedigree with female carriers showing mild to severe mental retardation. J Med Genet. 1982; 19(1):44-8. PMC: 1048818. DOI: 10.1136/jmg.19.1.44. View

13.

UCHIDA I, Joyce E . Activity of the fragile X in heterozygous carriers. Am J Hum Genet. 1982; 34(2):286-93. PMC: 1685287. View

14.

Chudley A, Knoll J, Gerrard J, Shepel L, McGahey E, Anderson J . Fragile (X) X-linked mental retardation I: relationship between age and intelligence and the frequency of expression of fragil (X)(q28). Am J Med Genet. 1983; 14(4):699-712. DOI: 10.1002/ajmg.1320140412. View

15.

NIELSEN K, Tommerup N, POULSEN H, Jacobsen P, Beck B, Mikkelsen M . Carrier detection and X-inactivation studies in the fragile X syndrome. Cytogenetic studies in 63 obligate and potential carriers of the fragile X. Hum Genet. 1983; 64(3):240-5. DOI: 10.1007/BF00279401. View

16.

UCHIDA I, Freeman V, Jamro H, Partington M, Soltan H . Additional evidence for fragile X activity in heterozygous carriers. Am J Hum Genet. 1983; 35(5):861-8. PMC: 1685813. View

17.

Wolff G, Hameister H, Ropers H . X-linked mental retardation: transmission of the trait by an apparently unaffected male. Am J Med Genet. 1978; 2(3):217-24. DOI: 10.1002/ajmg.1320020302. View