Analysis of genotype-phenotype correlations in human holoprosencephaly.
Since the discovery of the first gene causing holoprosencephaly (HPE), over 500 patients with mutations in genes associated with non-chromosomal, non-syndromic HPE have been described, with detailed descriptions available in over 300. Comprehensive clinical analysis of these individuals allows examination for the presence of genotype-phenotype correlations. These correlations allow a degree of differentiation between patients with mutations in different HPE-associated genes and for the application of functional studies to determine intragenic correlations. These early correlations are an important advance in the understanding of the clinical aspects of this disease, and in general argue for continued analysis of the genetic and clinical findings of large cohorts of patients with rare diseases in order to better inform both basic biological insight and care and counseling for affected patients and families.
Solomon
Benjamin D
BD
National Human Genome Research Institute, National Institutes of Health, Bethesda, MD 20892, USA.
Mercier
Sandra
S
Vélez
Jorge I
JI
Pineda-Alvarez
Daniel E
DE
Wyllie
Adrian
A
Zhou
Nan
N
Dubourg
Christèle
C
David
Veronique
V
Odent
Sylvie
S
Roessler
Erich
E
Muenke
Maximilian
M
D000818:Animals; D004252:DNA Mutational Analysis; D005838:Genotype; D053823:Hedgehog Proteins / Q000032:analysis / Q000235:genetics; D016142:Holoprosencephaly / Q000145:classification* / Q000175:diagnosis / Q000235:genetics*; D006801:Humans; D009687:Nuclear Proteins / Q000032:analysis / Q000235:genetics; D010641:Phenotype; D014157:Transcription Factors / Q000032:analysis / Q000235:genetics
D053823:Hedgehog Proteins; D009687:Nuclear Proteins; C509239:SHH protein, human; D014157:Transcription Factors; C491812:ZIC2 protein, human