PMID- 17480217
OWN - NLM
STAT- MEDLINE
DCOM- 20070517
LR  - 20220129
IS  - 1471-2350 (Electronic)
IS  - 1471-2350 (Linking)
VI  - 8
DP  - 2007 May 4
TI  - MRX87 family with Aristaless X dup24bp mutation and implication for polyAlanine 
      expansions.
PG  - 25
AB  - 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.
FAU - Laperuta, Carmela
AU  - Laperuta C
AD  - Institute of Genetics and Biophysics Adriano Buzzati Traverso CNR, Naples, Italy. 
      laperuta@igb.cnr.it
FAU - Spizzichino, Letizia
AU  - Spizzichino L
FAU - D'Adamo, Pio
AU  - D'Adamo P
FAU - Monfregola, Jlenia
AU  - Monfregola J
FAU - Maiorino, Antonio
AU  - Maiorino A
FAU - D'Eustacchio, Angela
AU  - D'Eustacchio A
FAU - Ventruto, Valerio
AU  - Ventruto V
FAU - Neri, Giovanni
AU  - Neri G
FAU - D'Urso, Michele
AU  - D'Urso M
FAU - Chiurazzi, Pietro
AU  - Chiurazzi P
FAU - Ursini, Matilde Valeria
AU  - Ursini MV
FAU - Miano, Maria Giuseppina
AU  - Miano MG
LA  - eng
GR  - TGM06S01/TI_/Telethon/Italy
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20070504
PL  - England
TA  - BMC Med Genet
JT  - BMC medical genetics
JID - 100968552
RN  - 0 (ARX protein, human)
RN  - 0 (DNA Primers)
RN  - 0 (Homeodomain Proteins)
RN  - 0 (Peptides)
RN  - 0 (Transcription Factors)
RN  - 25191-17-7 (polyalanine)
SB  - IM
MH  - *Chromosomes, Human, X
MH  - DNA Primers
MH  - *Gene Duplication
MH  - *Genetic Linkage
MH  - Homeodomain Proteins/*genetics
MH  - Humans
MH  - Male
MH  - Mental Retardation, X-Linked/*genetics
MH  - Mutation
MH  - Pedigree
MH  - Peptides/*genetics
MH  - Sequence Analysis, DNA
MH  - Transcription Factors/*genetics
PMC - PMC1868705
EDAT- 2007/05/08 09:00
MHDA- 2007/05/18 09:00
PMCR- 2007/05/04
CRDT- 2007/05/08 09:00
PHST- 2006/11/22 00:00 [received]
PHST- 2007/05/04 00:00 [accepted]
PHST- 2007/05/08 09:00 [pubmed]
PHST- 2007/05/18 09:00 [medline]
PHST- 2007/05/08 09:00 [entrez]
PHST- 2007/05/04 00:00 [pmc-release]
AID - 1471-2350-8-25 [pii]
AID - 10.1186/1471-2350-8-25 [doi]
PST - epublish
SO  - BMC Med Genet. 2007 May 4;8:25. doi: 10.1186/1471-2350-8-25.