PMID- 10995514
OWN - NLM
STAT- MEDLINE
DCOM- 20001026
LR  - 20190906
IS  - 0148-7299 (Print)
IS  - 0148-7299 (Linking)
VI  - 94
IP  - 3
DP  - 2000 Sep 18
TI  - Genotype-phenotype correlations and clinical diagnostic criteria in 
      Wolf-Hirschhorn syndrome.
PG  - 254-61
AB  - We report on a clinical-genetic study of 16 Wolf-Hirschhorn syndrome (WHS) 
      patients. Hemizygosity of 4p16.3 was detected by conventional prometaphase 
      chromosome analysis (11 patients) or by molecular probes on apparently normal 
      chromosomes (4 patients). One patient had normal chromosomes without a detectable 
      molecular deletion within the WHS "critical region." In each deleted patient, the 
      deletion was demonstrated to be terminal by fluorescence in situ hybridization 
      (FISH). The proximal breakpoint of the rearrangement was established by 
      prometaphase chromosome analysis in cases with a visible deletion. It was within 
      the 4p16.1 band in six patients, apparently coincident with the distal half of 
      this band in five patients. The extent of each of the four submicroscopic 
      deletions was established by FISH analyses with a set of overlapping cosmid 
      clones spanning the 4p16.3 region. We found ample variations in both the size of 
      the deletions and the position of the respective breakpoints. The precise 
      definition of the cytogenetic defect permitted an analysis of the 
      genotype-phenotype correlations in WHS, leading to the proposal of a set of 
      minimal diagnostic criteria, which in turn may facilitate the selection of 
      critical patients in the search for the gene(s) responsible for this disorder. We 
      observed that genotype-phenotype correlations in WHS mostly depend on the size of 
      the deletion, a deletion of <3.5 Mb resulting in a mild phenotype, in which 
      malformations are absent. The absence of a detectable molecular deletion is still 
      consistent with a WHS diagnosis. Based on these observations a "minimal" WHS 
      phenotype was inferred, the clinical manifestations of which are restricted to 
      the typical facial appearance, mild mental and growth retardation, and congenital 
      hypotonia.
CI  - Copyright 2000 Wiley-Liss, Inc.
FAU - Zollino, M
AU  - Zollino M
AD  - Istituto di Genetica Medica, Facolta di Medicina "A. Gemelli," UCSC, Rome, Italy. 
      mzollino@rm.unicatt.it
FAU - Di Stefano, C
AU  - Di Stefano C
FAU - Zampino, G
AU  - Zampino G
FAU - Mastroiacovo, P
AU  - Mastroiacovo P
FAU - Wright, T J
AU  - Wright TJ
FAU - Sorge, G
AU  - Sorge G
FAU - Selicorni, A
AU  - Selicorni A
FAU - Tenconi, R
AU  - Tenconi R
FAU - Zappala, A
AU  - Zappala A
FAU - Battaglia, A
AU  - Battaglia A
FAU - Di Rocco, M
AU  - Di Rocco M
FAU - Palka, G
AU  - Palka G
FAU - Pallotta, R
AU  - Pallotta R
FAU - Altherr, M R
AU  - Altherr MR
FAU - Neri, G
AU  - Neri G
LA  - eng
PT  - Journal Article
PL  - United States
TA  - Am J Med Genet
JT  - American journal of medical genetics
JID - 7708900
RN  - 0 (DNA Probes)
SB  - IM
MH  - Abnormalities, Multiple/*genetics
MH  - Adolescent
MH  - Brain/abnormalities
MH  - Child
MH  - Child, Preschool
MH  - *Chromosome Deletion
MH  - *Chromosomes, Human, Pair 4
MH  - Cosmids
MH  - DNA Probes
MH  - Developmental Disabilities/genetics
MH  - Facies
MH  - Female
MH  - Gene Deletion
MH  - Genotype
MH  - Humans
MH  - In Situ Hybridization, Fluorescence
MH  - Infant
MH  - Intellectual Disability/genetics
MH  - Karyotyping
MH  - Kidney/abnormalities
MH  - Male
MH  - Models, Genetic
MH  - Phenotype
MH  - Seizures/genetics
MH  - Syndrome
EDAT- 2000/09/20 11:00
MHDA- 2001/02/28 10:01
CRDT- 2000/09/20 11:00
PHST- 2000/09/20 11:00 [pubmed]
PHST- 2001/02/28 10:01 [medline]
PHST- 2000/09/20 11:00 [entrez]
AID - 10.1002/1096-8628(20000918)94:3<254::AID-AJMG13>3.0.CO;2-7 [pii]
AID - 10.1002/1096-8628(20000918)94:3<254::aid-ajmg13>3.0.co;2-7 [doi]
PST - ppublish
SO  - Am J Med Genet. 2000 Sep 18;94(3):254-61. doi: 
      10.1002/1096-8628(20000918)94:3<254::aid-ajmg13>3.0.co;2-7.