title: 14q13.1-21.1 deletion encompassing the HPE8 locus in an adolescent with intellectual disability and bilateral microphthalmia, but without holoprosencephaly.
abstract: Interstitial deletions involving 14q13.1q21.1 are rare. In the literature at least 10 cases involving this region have been described and all patients showed a phenotype within the holoprosencephaly (HPE) spectrum. Previous studies suggested the HPE8 region as a candidate locus for HPE at 14q13. We report an adolescent with a 14q13.1q21.1 deletion encompassing the HPE8 region associated with intellectual disability (ID), bilateral microphthalmia, and coloboma, without cerebral anomalies typical of HPE. Except for ocular defects (i.e., microphthalmia, coloboma) consistent with HPE-type anomalies, the minor facial dysmorphia was not suggestive for HPE and the absence of cerebral anomalies should rule out this diagnosis. The deletion of the potential HPE candidate genes NPAS3, EAPP, SNX6, and TULIP1, raises doubts about their pathologic role in determining HPE. It is likely that deletions of HPE genes are not sufficient to cause HPE, and that multiple genetic, chromosomal, and environmental factors interact to determine the variable clinical expression of HPE. This is the first case of a 14q deletion encompassing the HPE8 locus with the only features consistent with HPE-type anomalies affecting the ocular system (i.e., microphthalmia, coloboma), and without cerebral anomalies specific for HPE. The inclusion of potential HPE candidate genes in the deletion raises the question whether this patient is affected by a less severe form of HPE (HPE microform), or whether he has a new ID/MCA deletion syndrome.
authors.affiliation: Centro di Riferimento Regionale per la Sindrome di Down e le Altre Patologie Cromosomiche e Genetiche-Azienda Ospedaliera Ospedali Riuniti Villa Sofia-Cervello, Palermo, Italy. piccionemaria@libero.it
authors.forename: Maria
authors.initials: M
authors.lastname: Piccione
authors.forename: Gregorio
authors.initials: G
authors.lastname: Serra
authors.forename: Valeria
authors.initials: V
authors.lastname: Consiglio
authors.forename: Antonella
authors.initials: A
authors.lastname: Di Fiore
authors.forename: Simona
authors.initials: S
authors.lastname: Cavani
authors.forename: Marina
authors.initials: M
authors.lastname: Grasso
authors.forename: Michela
authors.initials: M
authors.lastname: Malacarne
authors.forename: Mauro
authors.initials: M
authors.lastname: Pierluigi
authors.forename: Chiara
authors.initials: C
authors.lastname: Viaggi
authors.forename: Giovanni
authors.initials: G
authors.lastname: Corsello
mesh_terms: D000293:Adolescent; D002883:Chromosomes, Human, Pair 14; D055028:Comparative Genomic Hybridization; D019066:Facies; D056426:Genetic Loci; D016142:Holoprosencephaly / Q000175:diagnosis; D006801:Humans; D017404:In Situ Hybridization, Fluorescence; D008607:Intellectual Disability / Q000175:diagnosis* / Q000235:genetics*; D008297:Male; D008850:Microphthalmos / Q000175:diagnosis* / Q000235:genetics*; D010641:Phenotype; D017384:Sequence Deletion