title: Holoprosencephaly: An update on cytogenetic abnormalities.
abstract: Holoprosencephaly (HPE), the most common developmental defect of the forebrain and midface, is caused by a failure of midline cleavage early in gestation. Isolated HPE, which is highly genetically heterogeneous, can be due to major chromosomal abnormalities. Initially, karyotype approach led to the identification of several recurrent chromosomal anomalies predicting different HPE loci. Subsequently, several genes were isolated from these critical HPE regions, but point mutations and deletions in these genes were found only in 25% of the genetic cases. In order to identify other HPE genes, a more accurate investigation of the genome in HPE patients was necessary. To date, high-resolution cytogenetic techniques such as subtelomeric multiplex ligation-dependent probe amplification (MLPA) and microarray-based comparative genomic hybridization (array CGH) have enhanced chromosomal aberration analysis. In this article, we have updated the cytogenetic anomalies associated with HPE in a map listing all the subtelomeric and interstitial deletions that have been characterized either by karyotype, MLPA, or array CGH. The accumulation of recurrent genomic imbalances will lead to the further delineation of minimal critical HPE loci, which is the first step to the identification of new HPE genes.
authors.affiliation: Institut National de la Santé et de la Recherche Médicale, Rennes, France.
authors.forename: Claude
authors.initials: C
authors.lastname: Bendavid
authors.forename: Valérie
authors.initials: V
authors.lastname: Dupé
authors.forename: Lucie
authors.initials: L
authors.lastname: Rochard
authors.forename: Isabelle
authors.initials: I
authors.lastname: Gicquel
authors.forename: Christèle
authors.initials: C
authors.lastname: Dubourg
authors.forename: Véronique
authors.initials: V
authors.lastname: David
mesh_terms: D002869:Chromosome Aberrations / Q000196:embryology; D055028:Comparative Genomic Hybridization / Q000379:methods; D005260:Female; D016142:Holoprosencephaly / Q000175:diagnosis* / Q000235:genetics*; D006801:Humans; D007621:Karyotyping / Q000379:methods; D046228:Microarray Analysis / Q000379:methods; D025202:Molecular Diagnostic Techniques; D011247:Pregnancy; D011296:Prenatal Diagnosis / Q000379:methods