Compound heterozygous female with fragile X syndrome

Abstract

We report on a 15-year-old compound heterozygous young woman with fragile X syndrome who has a full mutation of 363 repeats on one X chromosome and a premutation of 103 repeats on the other X chromosome. As predicted, subsequent testing demonstrated that her father carries a premutation (98 repeats) as does her mother (146 repeats). There is only one previous report of a compound heterozygous female with fragile X syndrome. By quantitation of Southern blot signals, the activation ratio for the premutation (the proportion of the premutation on the active X chromosome) was determined to be 0.78. Immunocytochemistry of blood smears showed fragile X mental retardation-1 protein (FMRP) expression in 63.5% of lymphocytes. Cognitively, this woman is functioning in the mid-range of involvement for fragile X females. She attends regular classes and receives supplemental assistance for her learning disabilities. She experiences behavior characteristics typical of females with fragile X syndrome including severe shyness, anxiety, panic episodes, mood swings, and attention deficits. She has responded very well to appropriate treatment including fluoxetine for anxiety, methylphenidate for attentional problems, and educational therapy.

Mixtures of poly(vinyl chloride) and copolyesters based on ε‐caprolactone and L‐lactide: Miscibility, thermal stability, and weathering resistance

“…This is a study of a unique sibling pair consisting of a 9‐year, 9‐month‐old male with a partially methylated full mutation and a 5‐year, 4‐month old female with a full mutation and a premutation (73) allele, a compound heterozygote with features of the PWP of FXS. There are several reports of females with compound heterozygous mutations [Mila et al, 1996; Russo et al, 1998; Linden et al, 1999; Hegde et al, 2001; Heine‐Suner et al, 2003; Martorell et al, 2011]. The female sibling reported here differs from the previously reported females because she is more severely affected, having a lower FSIQ than the reported females carrying premutation and full mutation alleles [Russo et al, 1998; Linden et al, 1999; Martorell et al, 2011].…”

“…There are several reports of females with compound heterozygous mutations [Mila et al, 1996; Russo et al, 1998; Linden et al, 1999; Hegde et al, 2001; Heine‐Suner et al, 2003; Martorell et al, 2011]. The female sibling reported here differs from the previously reported females because she is more severely affected, having a lower FSIQ than the reported females carrying premutation and full mutation alleles [Russo et al, 1998; Linden et al, 1999; Martorell et al, 2011]. However, one study reported on four sisters, all compound heterozygous, one of whom showed a complete inactivation of the chromosome carrying the premutation allele with consequent absence of FMRP and severe mental retardation [Martorell et al, 2011].…”

Unexpected finding of a paternal premutation of the fragile X FMR1 gene in a female fetus of a premutation carrier mother

“…The possible finding of compound heterozygosity in a female fetus, either pre‐/full mutation or pre‐/premutation, would pose an unusual counseling dilemma. A few cases of compound heterozygote females with a paternal premutation and a maternal full mutation have been reported [Milà et al, 1996; Russo et al, 1998; Linden et al, 1999; Hegde et al, 2001], some of whom present mental impairment. However, predicting prenatally the postnatal phenotype of such an individual would be challenging if not impossible.…”

Advances in research on the fragile X syndrome

“…Aziz and colleagues [1998] described six boys with either a fragile X pM (55-200 repeats) or an "intermediate" sized allele (41-54 repeats), and each demonstrated behavioral and intellectual features consistent with the syndrome phenotype, including autistic-like behaviors and other social difficulties. Less conclusive evidence is drawn from a report of a compound heterozygote with one fM and one pM whose psychological profile was similar to that of other females with the fM [Linden et al, 1999], including borderline intellectual functioning, rather than to that of males with fragile X syndrome. Mazzocco and Holden [1996] found that three sisters, each of who inherited two fragile X pM alleles, did not show cognitive disability.…”