Folate metabolism and chromosomal stability in the fragile X syndrome

Branda, Richard F.; Arthur, Diane C.; Woods, William G.; Danzl, Thomas J.; King, Richard A.

doi:10.1016/0002-9343(84)90349-8

Cited by 20 publications

(7 citation statements)

References 25 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…The 3p14 and 16q23 sites were the most common autosomal locations for breaks in cells from both control and fragile X syndrome individuals. In conclusion our results with a relatively large sample of control and fragile X syndrome individuals confirmed earlier reports (Vekemans et al 1983;Branda et al 1984) that no increased chromosome breakage exists in the fragile X syndrome individuals compared with control subjects. …”

supporting

confidence: 92%

Chromosome breakage in control and fragile X subjects using folate-deficient culture conditions

et al. 1988

View full text Add to dashboard Cite

The fragile X syndrome is a well-recognized form of X-linked mental retardation with a chromosomal fragile site at Xq27.3 observed in cells grown in folate-deficient culture medium (Brookwell and Turner 1983;Sutherland 1979;Chudley and Hagerman 1987). To determine if generalized chromosome instability exists in fragile X syndrome patients, 5793 lymphocytes from 55 control subjects (33 males and 22 females, average age 29.1 years with a range of 0.1 to 76 years) and 2731 lymphocytes from 27 fragile X syndrome individuals (21 males and 6 females, average age of 27.3 years with a range of 2 to 67 years) were studied in cultures with folate-deficient medium 199. The fragile X chromosome expression ranged from 1% to 55% with an average of 16%. In cells from the control subjects 85 chromosome breaks were observed with a frequency ranging from 0 to 14 (average 1.6) per 100 meta-phases. In cells from the fragile X syndrome patients 41 breaks were seen (excluding the Xq27 site) and the frequency ranged from 0 to 6 (average 1.5) per 100 metaphases. The site of the breaks was determined in banded chromosomes. The 3p14 and 16q23 sites were the most common autosomal locations for breaks in cells from both control and fragile X syndrome individuals. In conclusion our results with a relatively large sample of control and fragile X syndrome individuals confirmed earlier reports (Vekemans et al. 1983;Branda et al. 1984) that no increased chromosome breakage exists in the fragile X syndrome individuals compared with control subjects.

show abstract

supporting

confidence: 92%

Chromosome breakage in control and fragile X subjects using folate-deficient culture conditions

et al. 1988

View full text Add to dashboard Cite

show abstract

“…Although others [Branda et al, 1984;Gregory et al, 19861 have shown similar overall SCE rates for fragile X males and controls, attempts to identify the X chromosome to look specifically at the Xq27 site were not made. Our analysis of SCE at Xq27 suggested a significant increase in fragile X male cells grown in deficient medium compared to all other subjects.…”

Section: Discussionmentioning

confidence: 99%

Increased sister chromatid exchange frequency at Xq27 site in affected fragile X males

et al. 1987

View full text Add to dashboard Cite

Sister chromatid exchange (SCE) was evaluated in peripheral blood lymphocytes cultured from normal subjects, fragile X carrier females, and fragile X affected males and in general did not differ among all subjects whether cells were grown in thymidine-deficient or complete medium. However, at the Xq27 site, SCE was significantly increased for fragile X affected males, particularly in cells grown in thymidine-deficient medium.

show abstract

“…Clinically affected individuals can usually be diagnosed cytogenetically by an in vitro gap or break at Xq27 induced by media conditions that block the de novo thymidylic acid pathway (Sutherland 1979;Glover 1981;Tommerup et al 1981;Fonatsch 1981). However, there is no experimental evidence to suggest an in vivo defect in this biochemical pathway for fragile X subjects (Popovich et al 1983; Wang and Erbe 1984;Branda et al 1984).…”

Section: Indroductionmentioning

confidence: 99%

X chromosome imprinting in fragile�syndrome

Wenger

Steele

1990

Hum Genet

View full text Add to dashboard Cite

Laird et al. (1987) hypothesized that there are at least four cis-acting alleles or 'chromosome states' at Xq27 that increasingly delay replication at this chromosomal area resulting in its increasing fragility in vitro. When on the inactive X chromosome, the proposed third ('mutated') allele can permanently block reactivation of its cis Xq27 area as the chromosome passes through female meiosis. Males and some females who inherit such an 'imprinted' fragile X chromosome (the fourth proposed allele) will be clinically affected due to impaired transcription of genes in the 'imprinted' Xq27 area. To test this hypothesis, late replication reverse banding patterns at Xq27 were evaluated in cultured lymphoblastoid cell lines from 25 subjects. Our data suggest that DNA replication of the presumed 'imprinted' Xq27 region in affected fragile X patients is indeed later relative to Xq27 on the active X chromosome in other subjects. These results support in part Laird's hypothesis of chromosomal imprinting in fragile X syndrome.

show abstract

Folate metabolism and chromosomal stability in the fragile X syndrome

Cited by 20 publications

References 25 publications

Chromosome breakage in control and fragile X subjects using folate-deficient culture conditions

Chromosome breakage in control and fragile X subjects using folate-deficient culture conditions

Increased sister chromatid exchange frequency at Xq27 site in affected fragile X males

X chromosome imprinting in fragile�syndrome

Contact Info

Product

Resources

About