PMID- 24357569
OWN - NLM
STAT- MEDLINE
DCOM- 20141103
LR  - 20221207
IS  - 1552-4833 (Electronic)
IS  - 1552-4825 (Linking)
VI  - 164A
IP  - 3
DP  - 2014 Mar
TI  - Microarray and FISH-based genotype-phenotype analysis of 22 Japanese patients 
      with Wolf-Hirschhorn syndrome.
PG  - 597-609
LID - 10.1002/ajmg.a.36308 [doi]
AB  - Wolf-Hirschhorn syndrome (WHS) is a contiguous gene deletion syndrome of the 
      distal 4p chromosome, characterized by craniofacial features, growth impairment, 
      intellectual disability, and seizures. Although genotype-phenotype correlation 
      studies have previously been published, several important issues remain to be 
      elucidated including seizure severity. We present detailed clinical and 
      molecular-cytogenetic findings from a microarray and fluorescence in situ 
      hybridization (FISH)-based genotype-phenotype analysis of 22 Japanese WHS 
      patients, the first large non-Western series. 4p deletions were terminal in 20 
      patients and interstitial in two, with deletion sizes ranging from 2.06 to 29.42 
      Mb. The new Wolf-Hirschhorn syndrome critical region (WHSCR2) was deleted in all 
      cases, and duplication of other chromosomal regions occurred in four. Complex 
      mosaicism was identified in two cases: two different 4p terminal deletions; a 
      simple 4p terminal deletion and an unbalanced translocation with the same 4p 
      breakpoint. Seizures began in infancy in 33% (2/6) of cases with small (<6 Mb) 
      deletions and in 86% (12/14) of cases with larger deletions (>6 Mb). Status 
      epilepticus occurred in 17% (1/6) with small deletions and in 87% (13/15) with 
      larger deletions. Renal hypoplasia or dysplasia and structural ocular anomalies 
      were more prevalent in those with larger deletions. A new susceptible region for 
      seizure occurrence is suggested between 0.76 and 1.3 Mb from 4 pter, encompassing 
      CTBP1 and CPLX1, and distal to the previously-supposed candidate gene LETM1. The 
      usefulness of bromide therapy for seizures and additional clinical features 
      including hypercholesterolemia are also described.
CI  - (c) 2013 Wiley Periodicals, Inc.
FAU - Shimizu, Kenji
AU  - Shimizu K
AD  - Department of Medical Genetics, Shinshu University School of Medicine, Matsumoto, 
      Japan; Division of Medical Genetics, Saitama Children's Medical Center, Saitama, 
      Japan.
FAU - Wakui, Keiko
AU  - Wakui K
FAU - Kosho, Tomoki
AU  - Kosho T
FAU - Okamoto, Nobuhiko
AU  - Okamoto N
FAU - Mizuno, Seiji
AU  - Mizuno S
FAU - Itomi, Kazuya
AU  - Itomi K
FAU - Hattori, Shigeto
AU  - Hattori S
FAU - Nishio, Kimio
AU  - Nishio K
FAU - Samura, Osamu
AU  - Samura O
FAU - Kobayashi, Yoshiyuki
AU  - Kobayashi Y
FAU - Kako, Yuko
AU  - Kako Y
FAU - Arai, Takashi
AU  - Arai T
FAU - Tsutomu, Oh-ishi
AU  - Tsutomu OI
FAU - Kawame, Hiroshi
AU  - Kawame H
FAU - Narumi, Yoko
AU  - Narumi Y
FAU - Ohashi, Hirofumi
AU  - Ohashi H
FAU - Fukushima, Yoshimitsu
AU  - Fukushima Y
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20131219
PL  - United States
TA  - Am J Med Genet A
JT  - American journal of medical genetics. Part A
JID - 101235741
SB  - IM
MH  - Adolescent
MH  - Asian People/genetics
MH  - Child
MH  - Child, Preschool
MH  - Chromosome Aberrations
MH  - Chromosome Banding
MH  - Facies
MH  - Female
MH  - *Genetic Association Studies
MH  - Humans
MH  - *In Situ Hybridization, Fluorescence/methods
MH  - Infant
MH  - Japan
MH  - Male
MH  - *Oligonucleotide Array Sequence Analysis/methods
MH  - Phenotype
MH  - Wolf-Hirschhorn Syndrome/*diagnosis/*genetics
OTO - NOTNLM
OT  - 4p deletion
OT  - Wolf-Hirschhorn syndrome
OT  - fluorescence in situ hybridization (FISH)
OT  - genotype-phenotype correlation
OT  - microarray analysis
OT  - mosaicism
OT  - seizures
EDAT- 2013/12/21 06:00
MHDA- 2014/11/05 06:00
CRDT- 2013/12/21 06:00
PHST- 2013/04/27 00:00 [received]
PHST- 2013/09/30 00:00 [accepted]
PHST- 2013/12/21 06:00 [entrez]
PHST- 2013/12/21 06:00 [pubmed]
PHST- 2014/11/05 06:00 [medline]
AID - 10.1002/ajmg.a.36308 [doi]
PST - ppublish
SO  - Am J Med Genet A. 2014 Mar;164A(3):597-609. doi: 10.1002/ajmg.a.36308. Epub 2013 
      Dec 19.