MRX87 family with Aristaless X dup24bp mutation and implication for polyAlanine expansions

Cognitive impairments are heterogeneous conditions, and it is estimated that 10% may be caused by a defect of mental function genes on the X chromosome. One of those genes is Aristaless related homeobox (ARX) encoding a polyA-rich homeobox transcription factor essential for cerebral patterning and i...

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Bibliographic Details
Published in:BMC medical genetics 2007-05, Vol.8 (1), p.25-25
Main Authors: Laperuta, Carmela, Spizzichino, Letizia, D'Adamo, Pio, Monfregola, Jlenia, Maiorino, Antonio, D'Eustacchio, Angela, Ventruto, Valerio, Neri, Giovanni, D'Urso, Michele, Chiurazzi, Pietro, Ursini, Matilde Valeria, Miano, Maria Giuseppina
Format: Article
Language:English
Subjects:
Alanine
Causes of
Chromosomes, Human, X
DNA Primers
Gene Duplication
Gene mutations
Genetic aspects
Genetic Linkage
Homeobox genes
Homeodomain Proteins - genetics
Homeotic genes
Humans
Male
Mental Retardation, X-Linked - genetics
Mutation
Nervous system diseases
Pedigree
Peptides - genetics
Sequence Analysis, DNA
Transcription Factors - genetics
X chromosome
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Summary:Cognitive impairments are heterogeneous conditions, and it is estimated that 10% may be caused by a defect of mental function genes on the X chromosome. One of those genes is Aristaless related homeobox (ARX) encoding a polyA-rich homeobox transcription factor essential for cerebral patterning and its mutations cause different neurologic disorders. We reported on the clinical and genetic analysis of an Italian family with X-linked mental retardation (XLMR) and intra-familial heterogeneity, and provided insight into its molecular defect. We carried out on linkage-candidate gene studies in a new MRX family (MRX87). All coding regions and exon-intron boundaries of ARX gene were analysed by direct sequencing. MRX87 patients had moderate to profound cognition impairment and a combination of minor congenital anomalies. The disease locus, MRX87, was mapped between DXS7104 and DXS1214, placing it in Xp22-p21 interval, a hot spot region for mental handicap. An in frame duplication of 24 bp (ARXdup24) in the second polyAlanine tract (polyA_II) in ARX was identified. Our study underlines the role of ARXdup24 as a critical mutational site causing mental retardation linked to Xp22. Phenotypic heterogeneity of MRX87 patients represents a new observation relevant to the functional consequences of polyAlanine expansions enriching the puzzling complexity of ARXdup24-linked diseases.
ISSN:1471-2350
1471-2350
DOI:10.1186/1471-2350-8-25