Fragile X spectrum disorders

Reymundo Lozano, Carolina Alba Rosero, Randi J Hagerman

Research output: Contribution to journalReview article

79 Citations (Scopus)

Abstract

The fragile X mental retardation 1 gene (FMR1), which codes for the fragile X mental retardation 1 protein (FMRP), is located at Xp27.3. The normal allele of the FMR1 gene typically has 5 to 40 CGG repeats in the 5' untranslated region; abnormal alleles of dynamic mutations include the full mutation (> 200 CGG repeats), premutation (55-200 CGG repeats) and the gray zone mutation (45-54 CGG repeats). Premutation carriers are common in the general population with approximately 1 in 130-250 females and 1 in 250-810 males, whereas the full mutation and Fragile X syndrome (FXS) occur in approximately 1 in 4000 to 1 in 7000. FMR1 mutations account for a variety of phenotypes including the most common monogenetic cause of inherited intellectual disability (ID) and autism (FXS), the most common genetic form of ovarian failure, the fragile X-associated primary ovarian insufficiency (FXPOI, premutation); and fragile X-associated tremor/ataxia syndrome (FXTAS, premutation). The premutation can also cause developmental problems including ASD and ADHD especially in boys and psychopathology including anxiety and depression in children and adults. Some premutation carriers can have a deficit of FMRP and some unmethylated full mutation individuals can have elevated FMR1 mRNA that is considered a premutation problem. Therefore the term "Fragile X Spectrum Disorder" (FXSD) should be used to include the wide range of overlapping phenotypes observed in affected individuals with FMR1 mutations. In this review we focus on the phenotypes and genotypes of children with FXSD.

Original languageEnglish (US)
Pages (from-to)134-146
Number of pages13
JournalIntractable and Rare Diseases Research
Volume3
Issue number4
DOIs
StatePublished - Jan 1 2014

Fingerprint

Intellectual Disability
Mutation
Fragile X Mental Retardation Protein
Genes
Fragile X Syndrome
Phenotype
Alleles
Primary Ovarian Insufficiency
5' Untranslated Regions
Autistic Disorder
Psychopathology
Anxiety
Genotype
Depression
Messenger RNA
Population

Keywords

  • Autism spectrum disorder
  • Developmental delay
  • Fragile X syndrome
  • Intellectual disability
  • Premutation

ASJC Scopus subject areas

  • Medicine(all)

Cite this

Fragile X spectrum disorders. / Lozano, Reymundo; Rosero, Carolina Alba; Hagerman, Randi J.

In: Intractable and Rare Diseases Research, Vol. 3, No. 4, 01.01.2014, p. 134-146.

Research output: Contribution to journalReview article

Lozano, Reymundo ; Rosero, Carolina Alba ; Hagerman, Randi J. / Fragile X spectrum disorders. In: Intractable and Rare Diseases Research. 2014 ; Vol. 3, No. 4. pp. 134-146.
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