19q13.11 cryptic deletion: description of two new cases and indication for a role of WTIP haploinsufficiency in hypospadias
| Autor: | Vernon R. Sutton, Simone Gana, Weimin Bi, Pierangelo Veggiotti, Orsetta Zuffardi, Elena Rossi, G. Micieli, Katie Plunkett, Cristina Fedeli, Roberto Ciccone, Giusy Sciacca, Mohamad Maghnie, Anna Bersano |
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| Rok vydání: | 2012 |
| Předmět: |
Male
Ectodermal dysplasia Microcephaly Adolescent Developmental Disabilities Haploinsufficiency Biology Bioinformatics Article Intellectual Disability Genetics medicine Humans Child In Situ Hybridization Fluorescence Genetics (clinical) Zinc finger Comparative Genomic Hybridization Hypospadias sex disorders KRAB-ZNF genes Facies Wilms' tumor Microdeletion syndrome medicine.disease chromosome 19q13.11 deletion syndrome DNA-Binding Proteins array-CGH ATPases Associated with Diverse Cellular Activities Female Chromosome Deletion Carrier Proteins Chromosomes Human Pair 19 WTIP gene Comparative genomic hybridization |
| Zdroj: | European Journal of Human Genetics |
| ISSN: | 1476-5438 1018-4813 |
| DOI: | 10.1038/ejhg.2012.19 |
| Popis: | Developmental delay/intellectual disabilities, speech disturbance, pre- and postnatal growth retardation, microcephaly, signs of ectodermal dysplasia, and genital malformations in males (hypospadias) represent the phenotypic core of the recent emerging 19q13.11 deletion syndrome. Using array-CGH for genome-wide screening we detected an interstitial deletion of chromosome band 19q13.11 in two patients exhibiting the recognizable pattern of malformations as described in other instances of this submicroscopic genomic imbalance. The deletion detected in our patients has been compared with previously reported cases leading to the refinement of the minimal overlapping region (MOR) for this microdeletion syndrome to 324 kb. This region encompasses five genes: four zinc finger (ZNF) genes belonging to the KRAB-ZNF subfamily (ZNF302, ZNF181, ZNF599, and ZNF30) and LOC400685. On the basis of our male patient 1 and on further six male cases of the literature, we also highlighted that larger 19q13.11 deletions including the Wilms tumor interacting protein (WTIP) gene, proximal to the MOR, results in hypospadias making this gene a possible candidate for this genital abnormality due to its well-known interaction with WT1. Although the mechanism underlying the phenotypic effects of copy number alterations involving KRAB-ZNF genes at 19q13.11 has not clearly been established, we suggest their haploinsufficiency as the most likely candidate for the phenotypic core of the 19q13.11 deletion syndrome. In addition, we hypothesized WTIP gene haploinsufficiency as responsible for hypospadias. |
| Databáze: | OpenAIRE |
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