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Contractions in the second polyA tract of ARX are rare, non‐pathogenic polymorphisms
Author(s) -
Conti Valerio,
Marini Carla,
Mei Davide,
Falchi Melania,
Ferrari Anna Rita,
Guerrini Renzo
Publication year - 2011
Publication title -
american journal of medical genetics part a
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.064
H-Index - 112
eISSN - 1552-4833
pISSN - 1552-4825
DOI - 10.1002/ajmg.a.33753
Subject(s) - homeobox , biology , genetics , phenotype , exon , gene duplication , contraction (grammar) , polymorphism (computer science) , epilepsy , gene , west syndrome , mutation , transcription factor , endocrinology , genotype , neuroscience
Aristaless related homeobox (ARX) is a transcription factor containing highly conserved octapeptide, homeobox, acidic, and aristaless domains, as well as four polyA tracts. The most frequent ARX mutation found to date in patients with X‐linked infantile spasms, Partington syndrome or X‐linked mental retardation, is a duplication of 24 bp in exon 2, resulting in the expansion of the second polyA tract. Although the pathogenic role of this expansion has been well characterized, the effect of contractions in the same polyA tract is still debated since different reports have associated contractions to either mental retardation or a normal phenotype. Here, we report two unrelated girls with epilepsy and mental retardation who inherited from their unaffected parents, of either sex, a deletion of 24 bp (c.441_464del), resulting in a contraction of eight alanines in the second polyA tract of ARX. Segregation studies revealed the c.441_464del also in two healthy relatives of one of the patients. This finding supports the hypothesis that this contraction represents a rare, benign polymorphism. © 2010 Wiley‐Liss, Inc.