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last update : 23-04-2012
Symbol ATRX
Location Xq13.3
Name alpha thalassemia / mental retardation syndrome, X-linked, non deletion type
Other name(s)
  • ATRX syndrome
  • XLMR - hypotonic face syndrome
  • Corresponding gene ATRX
    Other symbol(s) ATR-X, ATR2, HMRDX
    Main clinical features
  • severe developmental impairment and mental retardation, with hypotonia as a hallmark of the condition
  • distinctive cranio-facial features including small head, hypertelorism, small nose with retracted columella, protruding lower lip, coarse facies
  • genital anomalies with under masculinization and ambiguous or female external genitalia in some patients
  • short stature with minor skeletal anomalies
  • alpha-thalassemia (HbB)
  • agenesis of corpus callosum
  • Genetic determination sex linked
    Prevalence over 150 affected individuals known
    Function/system disorder metabolism/porphyrin and heme
    mental retardation
    Type disease
    Gene mutationChromosome rearrangementEffectComments
    repeat expansion   unknown dup24 is the most frequent mutation, resulting in elongation of polyalanine tract from 12 to 20 Ala, in familial forms, associated to DNA methylation defects
    various types     most mutations are detected in the zinc finger motif (65 percent) and the helicase domain (35 percent)
    various types   abnormal protein/loss of function alter ATRX targeting to promyelocytic leukemia nuclear bodies
  • ATRX is the only gene associated with ATRX syndrome, unaffected female carriers have skewed X-chromosome inactivation
  • half of all of the disease-associated missense mutations cluster in a cysteine-rich region in the N terminus of ATRX (the ADD) domain)
  • 82 missense mutations found in patients with ATRX syndrome are almost exclusively confined to its N-terminal PHD-like domain (known as the ADD domain) and the conserved Snf2 domain
  • . approximately 50p100 of the missense mutations in affected persons are clustered in a cysteine-rich domain termed ADD (ATRX-DNMT3-DNMT3L) (PMID: 21666679))