Collaborative prospective study of the fragile X syndrome: One‐year progress report

Sherman, S. L.; Barbi, Gotthold; Brøndum‐Nielsen, Karen; Brown, W. Ted; Nj, Carpenter; Chudley, AE; Ferraz, O. P.; Ferreira, Pedro Ruan Chaves; Gustavson, K.-H.; Halliday, Jane; Hockey, Athel; Howard‐Peebles, P. N.; Jenkins, Edmund C.; Kennerknecht, [No Value]; Kähkönen, Marketta; Ladaique, P; Leisti, J; Maddalena, Anne; Mazurczak, Tadeusz; Jf, Mattéi; Mattina, Teresa; McKinley, MJ; Murphy, Patricia D.; Mc, Pellissier; Purvis‐Smith, Stuart; Robinson, Hazel M.; Scapagnini, U; Schaap, Tamar; Lr, Shapiro; Smits, A. P. T.; Steinbach, Peter; Turner, Gillian; Ia, Uchida; Vanoost, Ba; Ma, Voelckel; Webb, T.

doi:10.1002/ajmg.1320430155

Cited by 7 publications

(4 citation statements)

References 8 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…However, if we consider severe MR (SMR), as defined by an IQ<50, prevalence rates are more homogeneous, and several recent studies (Schaefer and Bodensteiner 1992, Mlika et al 1993 have given values of around 3 per 1000 children. Generally, epidemiological research concerning MR only looks at specific subgroups, such as X-linked MR, idiopathic MR, cases associated with motor deficiency, or congenital anomalies (Ohdo et al 1992, Sherman et al 1992, Boutin et al 1995.…”

mentioning

confidence: 99%

Aetiological findings and associated factors in children with severe mental retardation

Cans¹,

Wilhelm²,

Baille³

et al. 1999

Develop Med Child Neuro

View full text Add to dashboard Cite

The purpose of this study, through a retrospective epidemiological survey carried out over three geographical areas in France, was to characterize the aetiological factors involved in severe mental retardation (SMR) within a geographically defined population of children with disabilities aged between 7 and 16 years. The inclusion criteria for SMR (IQ<50) were met by 1150 children born between 1976 and 1985. Of these children, aetiology was known in 25%, suspected (or unclear) in 26%, and unknown in 49%. These rates of known and suspected aetiology varied between the groups of children with CP and those without CP. An analysis of factors associated with SMR was undertaken among the 144 subjects with SMR, of suspected or unknown aetiology, who had been referred to a neonatal care unit with or without intensive care (NCU) during their neonatal period. These subjects with SMR were compared with 864 children without SMR (control children) who were also referred to an NCU during their neonatal period. The main specific associated factors were a prolonged intubation of more than 24 hours, a very low birthweight (<1500 g) for children with an associated clinical feature of CP, and the presence of isolated neonatal fits and a time of transfer to the NCU of more than 4 hours after birth for children without an associated clinical feature of CP. Although common associated factors were encountered in the children with SMR with CP and the children with SMR without CP, the results of this study suggest differences in the underlying pathogenic factors.

show abstract

mentioning

confidence: 99%

Aetiological findings and associated factors in children with severe mental retardation

Cans¹,

Wilhelm²,

Baille³

et al. 1999

Develop Med Child Neuro

View full text Add to dashboard Cite

show abstract

“…Although extensive somatic mosaicism was detected from the CVS of the atrisk fetus, it could not be determined whether the fetus would be mentally retarded. Since the mother was a phenotypically normal premutation carrier, the recurrence risk of mental retardation in the fetus may be lower than in a fetus of a mentally retarded mother (Sherman et al 1992). About 50% of female carriers of the fragile X full mutation were reported not to exhibit mental retardation (Tejada et al 1992).…”

Section: Resultsmentioning

confidence: 99%

Prenatal diagnosis of fragile X syndrome by direct detection of the dynamic mutation due to an unstable DNA sequence

Yamauchi¹,

Nagata

Seki

et al. 1993

Clinical Genetics

View full text Add to dashboard Cite

Yamauchi M, Nagata S, Seki N, Toyama Y, Harada N, Niikawa N, Masuno I, Kajii T, Hori T. Prenatal diagnosis of fragile X syndrome by direct detection of the dynamic mutation due to an unstable DNA sequence. Clin Genet 1993: 44: 169–172. © Munksgaard, 1993 The fragile X syndrome is the most common familial form of mental retardation. The mutation causing the syndrome is dynamic mutation due to an unstable DNA (CCG)n repeat localized at Xq27.3. We have previously reported a PCR procedure to prepare a diagnostic probe, pPCRfx1, which can be used to determine the genotype of fragile X mutation individuals by Southern blot analysis. In the present study, pPCRfx1 was applied to the prenatal diagnosis, using chorionic villus cells, of a fetus which was at risk of having fragile X syndrome. In the PstI assay, the Southern blot showed the typical pattern of a female carrier with the full mutation. Analysis of the DNA methylation patterns by EcoRI + EagI assay showed that the EagI restriction site was not methylated on the mutated X chromosome of chorionic villi, but the sites were totally methylated in the brain and other tissues of the fetus. Thus the fetus was diagnosed to be a heterozygous female carrier of the dynamic mutation involved in the fragile X syndrome.

show abstract

“…Another interesting issue is the inheritance of a full mutation or large premutation. It is assumed that the normal and mutated alleles are equally likely to be passed on, which may also be incorrect [26]. The retrospective nature of pedigree analysis within affected families can lead to a biased estimate of the expansion risk.…”

Section: Discussionmentioning

confidence: 99%

“…Normally she is unaware of her carrier status – premutations are usually not associated with any clinical phenotype – and unaware that her premutation during pregnancy may expand to a full mutation in her offspring, leading to mental retardation [23]. Several groups have published regarding the risk of expansion of a full mutation from a premutation [18,20,24] and Sherman et al [25,26] have previously carried out prospective studies in this field.…”

mentioning

confidence: 99%

Prenatal diagnosis of fragile X syndrome and the risk of expansion of a premutation

2000

View full text Add to dashboard Cite

The aim of the present study was to evaluate prospectively the dynamics of the FMR1 gene. The risk of full mutation among pregnant women and the carriers, and the risk of expansion of a premutation allele to a full mutation were estimated. We identified 89 pregnant women with an expanded FMR1 gene seeking prenatal diagnosis. Amniocentesis or chorion villus sampling (CVS) was offered and a DNA test of the FMR1 gene was carried out in such pregnancies. The overall risk of full mutation among women (N = 21) with a repeat size between 60 and 80 was 4.8% (one fetus with mosaicism), and the risk of expansion of the premutation allele to a full mutation was 14% in those offspring to whom the premutation allele was transmitted. The risk of full mutation among the carriers (N = 13) with a repeat size between 81 and 100 was 61.5% (8/13), and the risk of expansion of a premutation allele to a full mutation was 89%. Only one case fell into the category of 101-200 repeats, and expansion to a full mutation was recorded. Fetuses of full mutation mothers inherited the larger allele in 64% (14/22) of the cases. The range of 40-59 repeats was safe: there were no fetal full mutations. The risk of full mutation was also low among the subjects with a repeat size between 60 and 80, whereas the risk increased significantly after 80 repeats. Maternal premutation size was positively correlated with the risk of having a full mutation offspring.

show abstract

Collaborative prospective study of the fragile X syndrome: One‐year progress report

Cited by 7 publications

References 8 publications

Aetiological findings and associated factors in children with severe mental retardation

Aetiological findings and associated factors in children with severe mental retardation

Prenatal diagnosis of fragile X syndrome by direct detection of the dynamic mutation due to an unstable DNA sequence

Prenatal diagnosis of fragile X syndrome and the risk of expansion of a premutation

Contact Info

Product

Resources

About