PMID- 28150386
OWN - NLM
STAT- MEDLINE
DCOM- 20170629
LR  - 20180628
IS  - 1098-1004 (Electronic)
IS  - 1059-7794 (Linking)
VI  - 38
IP  - 5
DP  - 2017 May
TI  - An Emerging Female Phenotype with Loss-of-Function Mutations in the 
      Aristaless-Related Homeodomain Transcription Factor ARX.
PG  - 548-555
LID - 10.1002/humu.23190 [doi]
AB  - The devastating clinical presentation of X-linked lissencephaly with abnormal 
      genitalia (XLAG) is invariably caused by loss-of-function mutations in the 
      Aristaless-related homeobox (ARX) gene. Mutations in this X-chromosome gene 
      contribute to intellectual disability (ID) with co-morbidities including seizures 
      and movement disorders such as dystonia in affected males. The detection of 
      affected females with mutations in ARX is increasing. We present a family with 
      multiple affected individuals, including two females. Two male siblings 
      presenting with XLAG were deceased prior to full-term gestation or within the 
      first few weeks of life. Of the two female siblings, one presented with 
      behavioral disturbances, mild ID, a seizure disorder, and complete agenesis of 
      the corpus callosum (ACC), similar to the mother's phenotype. A novel insertion 
      mutation in Exon 2 of ARX was identified, c.982delCinsTTT predicted to cause a 
      frameshift at p.(Q328Ffs(*) 37). Our finding is consistent with loss-of-function 
      mutations in ARX causing XLAG in hemizygous males and extends the findings of ID 
      and seizures in heterozygous females. We review the reported phenotypes of 
      females with mutations in ARX and highlight the importance of screening ARX in 
      male and female patients with ID, seizures, and in particular with complete ACC.
CI  - (c) 2017 WILEY PERIODICALS, INC.
FAU - Mattiske, Tessa
AU  - Mattiske T
AD  - Department of Paediatrics, School of Medicine, University of Adelaide, Adelaide, 
      SA, Australia.
AD  - Robinson Research Institute, University of Adelaide, Adelaide, SA, Australia.
FAU - Moey, Ching
AU  - Moey C
AD  - Department of Paediatrics, School of Medicine, University of Adelaide, Adelaide, 
      SA, Australia.
AD  - Robinson Research Institute, University of Adelaide, Adelaide, SA, Australia.
FAU - Vissers, Lisenka E
AU  - Vissers LE
AD  - Department of Human Genetics, Donders Institute for Brain, Cognition, and 
      Behaviour, Radboud University Medical Center, Nijmegen, the Netherlands.
FAU - Thorne, Natalie
AU  - Thorne N
AD  - Murdoch Children's Research Institute, Melbourne, Australia.
AD  - University of Melbourne, Melbourne, Australia.
AD  - Melbourne Genomics Health Alliance, Melbourne, Australia.
FAU - Georgeson, Peter
AU  - Georgeson P
AD  - Melbourne Genomics Health Alliance, Melbourne, Australia.
AD  - Victorian Life Sciences Computation Initiative, The University of Melbourne, 
      Melbourne, Australia.
FAU - Bakshi, Madhura
AU  - Bakshi M
AD  - Department of Clinical Genetics, Liverpool Hospital, Liverpool, NSW, Australia.
FAU - Shoubridge, Cheryl
AU  - Shoubridge C
AD  - Department of Paediatrics, School of Medicine, University of Adelaide, Adelaide, 
      SA, Australia.
AD  - Robinson Research Institute, University of Adelaide, Adelaide, SA, Australia.
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20170215
PL  - United States
TA  - Hum Mutat
JT  - Human mutation
JID - 9215429
RN  - 0 (ARX protein, human)
RN  - 0 (Homeodomain Proteins)
RN  - 0 (Transcription Factors)
SB  - IM
MH  - Abnormalities, Multiple/diagnosis/genetics
MH  - Brain/pathology
MH  - Child
MH  - Child, Preschool
MH  - DNA Mutational Analysis
MH  - Exons
MH  - Female
MH  - Genes, X-Linked
MH  - *Genetic Association Studies
MH  - Homeodomain Proteins/*genetics/metabolism
MH  - Humans
MH  - Magnetic Resonance Imaging
MH  - Male
MH  - Middle Aged
MH  - *Mutation
MH  - Pedigree
MH  - *Phenotype
MH  - Transcription Factors/*genetics/metabolism
OTO - NOTNLM
OT  - ARX
OT  - Aristaless-related homeobox
OT  - LISX2
OT  - X-linked lissencephaly
OT  - X-linked lissencephaly-2
OT  - XLAG
OT  - intellectual disability
OT  - seizure
EDAT- 2017/02/06 06:00
MHDA- 2017/07/01 06:00
CRDT- 2017/02/03 06:00
PHST- 2016/09/20 00:00 [received]
PHST- 2016/12/18 00:00 [revised]
PHST- 2017/01/24 00:00 [accepted]
PHST- 2017/02/06 06:00 [pubmed]
PHST- 2017/07/01 06:00 [medline]
PHST- 2017/02/03 06:00 [entrez]
AID - 10.1002/humu.23190 [doi]
PST - ppublish
SO  - Hum Mutat. 2017 May;38(5):548-555. doi: 10.1002/humu.23190. Epub 2017 Feb 15.