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Open Access Research article

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

Carmela Laperuta1, Letizia Spizzichino2, Pio D'Adamo3, Jlenia Monfregola1, Antonio Maiorino4, Angela D'Eustacchio3, Valerio Ventruto1, Giovanni Neri2, Michele D'Urso1, Pietro Chiurazzi2, Matilde Valeria Ursini1 and Maria Giuseppina Miano1*

Author Affiliations

1 Institute of Genetics and Biophysics "Adriano Buzzati Traverso" CNR, Naples, Italy

2 Catholic University of Rome, Rome, Italy

3 Telethon Institute of Genetics and Medicine, TIGEM, Naples, Italy

4 C.A.R.S.I.C Institute, Venafro, Italy

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BMC Medical Genetics 2007, 8:25  doi:10.1186/1471-2350-8-25

Published: 4 May 2007

Abstract

Background

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.

Methods

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.

Results

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.

Conclusion

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.