High functioning male with fragile X syndrome and fragile X-associated tremor/ataxia syndrome

Kirin Basuta, Andrea Schneider, Louise Gane, Jonathan Polussa, Bryan K Woodruff, Dalyir Pretto, Randi Hagerman, Flora Tassone

Research output: Contribution to journalArticle

16 Citations (Scopus)

Abstract

Fragile X syndrome (FXS) affects individuals with more than 200 CGG repeats (full mutation) in the fragile X mental retardation 1 (FMR1) gene. Those born with FXS experience cognitive and social impairments, developmental delays, and some features of autism spectrum disorders. Carriers of a premutation (55-200 CGG repeats) are generally not severely affected early in life; however, are at high risk of developing the late onset neurodegenerative disorder, Fragile X-associated Tremor/Ataxia Syndrome (FXTAS), or Fragile X-associated Primary Ovarian Insufficiency (FXPOI), and may have other medical conditions such as developmental delay, autism spectrum disorders, hypertension, anxiety, and immune-mediated disorders. Here we present a case of a 58-year-old man with a borderline IQ, average memory skills, and executive function deficits. He met criteria for multiple psychiatric diagnoses and presented with tremor and ataxia, meeting criteria for FXTAS. Molecular testing unveiled a completely unmethylated FMR1 full mutation in peripheral blood mononucleated cells with elevated FMR1 mRNA and premutation alleles of different sizes in two other tissues (primary fibroblasts and sperm), indicating the presence of allele instability based on both inter- and intra-tissue mosaicism. The observation of FXTAS in this case of a full mutation mosaic man suggests that the pathogenic mechanism underlying this disorder is not observed exclusively in premutation carriers as it was originally thought. The concomitant presence of features of FXS and late onset neurological deterioration with probable FXTAS likely result from a combined molecular pathology of elevated FMR1 mRNA levels, a molecular hallmark of FXTAS and low FMRP expression that leads to FXS.

Original languageEnglish (US)
Pages (from-to)2154-2161
Number of pages8
JournalAmerican Journal of Medical Genetics, Part A
Volume167
Issue number9
DOIs
StatePublished - Sep 1 2015

Fingerprint

Fragile X Syndrome
Intellectual Disability
Mutation
Alleles
Primary Ovarian Insufficiency
Messenger RNA
Mosaicism
Molecular Pathology
Immune System Diseases
Executive Function
Tremor
Ataxia
Mental Disorders
Neurodegenerative Diseases
Spermatozoa
Blood Cells
Anxiety
Fibroblasts
Observation
Fragile X Tremor Ataxia Syndrome

Keywords

  • Fragile X syndrome
  • FXTAS

ASJC Scopus subject areas

  • Genetics(clinical)
  • Genetics

Cite this

High functioning male with fragile X syndrome and fragile X-associated tremor/ataxia syndrome. / Basuta, Kirin; Schneider, Andrea; Gane, Louise; Polussa, Jonathan; Woodruff, Bryan K; Pretto, Dalyir; Hagerman, Randi; Tassone, Flora.

In: American Journal of Medical Genetics, Part A, Vol. 167, No. 9, 01.09.2015, p. 2154-2161.

Research output: Contribution to journalArticle

Basuta, K, Schneider, A, Gane, L, Polussa, J, Woodruff, BK, Pretto, D, Hagerman, R & Tassone, F 2015, 'High functioning male with fragile X syndrome and fragile X-associated tremor/ataxia syndrome', American Journal of Medical Genetics, Part A, vol. 167, no. 9, pp. 2154-2161. https://doi.org/10.1002/ajmg.a.37125
Basuta, Kirin ; Schneider, Andrea ; Gane, Louise ; Polussa, Jonathan ; Woodruff, Bryan K ; Pretto, Dalyir ; Hagerman, Randi ; Tassone, Flora. / High functioning male with fragile X syndrome and fragile X-associated tremor/ataxia syndrome. In: American Journal of Medical Genetics, Part A. 2015 ; Vol. 167, No. 9. pp. 2154-2161.
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