Population screening at the FRAXA and FRAXE loci: molecular analyses of boys with learning difficulties and their mothers

Murray, Anna; Youings, Sheila; Dennis, N R; Latsky, Lorinda; Linehan, Paul; McKechnie, Nicky; Macpherson, James; Pound, Michelle; Jacobs, Patricia A.

doi:10.1093/hmg/5.6.727

Cited by 147 publications

(153 citation statements)

References 40 publications

(57 reference statements)

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“…In addition we have reported an excess of intermediate (41-60 repeats) FRAXA alleles in a group of boys with non-specific learning difficulty, suggesting that even relatively small expansions in FMR1 may have a phenotypic effect. 16 In women who are still cycling we have demonstrated an increased level of serum FSH in the premutation group compared with controls. 13 In a small pilot study Braat et al 17 reported the hormonal profiles of nine premutation carriers under age 40 and found levels suggestive of ovarian failure in eight of them.…”

Section: Discussionmentioning

confidence: 69%

Reproductive and menstrual history of females with fragile X expansions

Ennis²,

et al. 2000

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FRAXA premutations have been associated with premature ovarian failure (POF) or menopause before the age of 40. We have studied women in families ascertained because of a mentally retarded full mutation relative and determined their age of menopause, serum hormone levels in premenopausal individuals and the outcome of any pregnancies. Survival analysis was used as a measure of menopause and demonstrated a significant decrease in age of menopause in premutation carriers compared with their full mutation carrier and normal relatives. Serum FSH was also raised in premutation carriers, although oestradiol, inhibin A and inhibin B were not significantly different. However, we did not find an excess of dizygous twins or pregnancy loss/trisomies, both of which are associated with aging ovaries. Thus premutation carriers as a group have an earlier menopause and raised serum FSH but do not appear to manifest other features of an aging ovary.

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Section: Discussionmentioning

confidence: 69%

Reproductive and menstrual history of females with fragile X expansions

Ennis²,

et al. 2000

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“…Indeed, differences in FRAXA repeat distributions have been reported between several ethnic groups, even among Caucasians. 13,20,21 Furthermore, the lack of consensus about the IA range definition increases this variability among analysed populations. In the present study, we used an IA range between 45 and 54 repeats, being the same for patients and controls.…”

Section: Discussionmentioning

confidence: 99%

Intermediate FMR1 alleles and cognitive and/or behavioural phenotypes

et al. 2011

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During the last few years, several studies have reported an excess of intermediate FMR1 alleles in patients with cognitive and/or behavioural phenotypes. Here, we report the frequency of intermediate alleles (IAs) in three pathologies, intellectual disabilities (IDs), attention-deficit/hyperactivity disorder and autism, from different Spanish regions. We found 142 IAs among 9015 patients with ID (1.6%), 4 among the 415 ADHD patients (0.96%) and 4 among the 300 autistic patients (1.3%), similar to the frequency reported in our control population. No evidence was found of an excess of IA at the FRAXA locus in any of the study populations, although geographical variability was detected. Moreover, the analysis of 100 transmissions of IAs showed that 95% of these alleles were stable. Only 3% expanded within the same range and 2% expanded to a full mutation in two generations. No evidence of an association between IAs and behavioural or cognitive phenotypes was found, suggesting that IAs are not clearly implicated in these pathologies.

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“…After the molecular characterization of the FRAXE fragile site and its possible implications in learning difficulties a number of special education need and development or language delayed group of children were evaluated for the presence of FRAXE expansions (Allingham-Hawkins and Ray 1995; Chan and Wong 1998; Gécz 2000; Knight et al 1996;Milà et al 1997;Murray et al 1996;Youings et al 2000). Putting all the data together, from a large sample of higher than 13,000 individuals with mental retardation/ID, only seven FRAXE full expansions were identified.…”

Section: Discussionmentioning

confidence: 99%

Autism Spectrum Disorder: FRAXE Mutation, a Rare Etiology

Correia

Café

Almeida

et al. 2014

J Autism Dev Disord

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Autism spectrum disorder (ASD) is characterized by impaired social interaction and communication, restricted interests and repetitive behaviors. Fragile X E is associated with X-linked non-specific mild intellectual disability (ID) and with behavioral problems. Most of the known genetic causes of ASD are also causes of ID, implying that these two identities share common genetic bases. We present a child with an ASD with a normal range of intelligence quotient, that later evolved to compulsive behavior. FRAXE locus analysis by polymerase chain reaction revealed a complete mutation of the FMR 2 gene. This report stresses the importance of clinicians being aware of the association between a full mutation of FMR2 and ASD associated with compulsive behavior despite normal intellectual level.We present a boy who was the first child of healthy, unrelated parents. He was born at 36 gestational weeks by cesarean section. His pre-natal growth was in 5th Percentile in weight (2,680 g), height (47 cm) and head circumference (32.5 cm). The Apgar score was 5 in the first minute and 9 in the fifth. Early postnatal history was normal. Early motor skills were acquired at normal age range, but walking age was delayed until 18 months old. The first parental concerns were evident in the third year of life exhibiting mild language development delay (first words by 24 months of age and phrases at 30) as well as marked behavioral problems characterized by psychomotor agitation and compulsions. Echolalia and verbiage became more obvious with age. In addition, autistic features, such as restricted interests, repetitive behavior and impaired social interaction mainly with other children were also present. When he started pre-school at 3 years old, teachers mentioned that he was isolated, lacked social reciprocity and had major misunderstandings of social cues. He also exhibited various stereotyped behaviors associated with restricted interests. Despite his difficulty to integrate at school, he was good with numbers, sequencing, memory and reasoning. He showed no autonomy in group activities, most of the times looking for an adult to help him. Moreover, this child had an ongoing concern with gas cylinders and electricity. Seizures were never observed.He was referred at the age of 7 years old to a neurodevelopment outpatient clinic in a tertiary Pediatric

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Population screening at the FRAXA and FRAXE loci: molecular analyses of boys with learning difficulties and their mothers

Cited by 147 publications

References 40 publications

Reproductive and menstrual history of females with fragile X expansions

Reproductive and menstrual history of females with fragile X expansions

Intermediate FMR1 alleles and cognitive and/or behavioural phenotypes

Autism Spectrum Disorder: FRAXE Mutation, a Rare Etiology

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