Periventricular nodular heterotopia and Williams syndrome
Russell J Ferland1, John N Gaitanis, Kira Apse
1Department of Biology, Rensselaer Polytechnic Institute, Center for Biotechnology and Interdisciplinary Studies, Troy, New York, USA.
American Journal of Medical Genetics. Part A
|May 13, 2006
Summary
This study details the first child diagnosed with both periventricular nodular heterotopia (PNH) and Williams syndrome. Genetic analysis revealed a deletion on chromosome 7q11.23, suggesting a new PNH disorder.
Area of Science:
- Neurogenetics
- Developmental Biology
- Genomic Medicine
Background:
- Periventricular nodular heterotopia (PNH) is a rare congenital brain malformation characterized by misplaced gray matter.
- Williams syndrome is a genetic disorder known for cardiovascular issues, distinct facial features, and developmental delays.
- The genetic underpinnings of PNH are diverse, with mutations in the FLNA gene being a common cause.
Observation:
- This report presents the first documented case of a pediatric patient exhibiting both bilateral PNH and Williams syndrome.
- Initial investigations utilized fluorescent in situ hybridization (FISH) to analyze the Williams syndrome critical region (WSCR).
Findings:
- FISH analysis confirmed a deletion of the elastin gene within the WSCR.
- Further high-resolution genetic mapping, including loss of heterozygosity analysis via microsatellite markers and single nucleotide polymorphism (SNP) profiling, identified a 1.5 Mb deletion extending telomerically beyond the standard WSCR.
- Crucially, no mutations were found in the X-linked filamin-A (FLNA) gene, ruling out this frequent cause of PNH.
Implications:
- These findings implicate a novel dominant PNH disorder associated with chromosome 7q11.23.
- This discovery expands the known genetic landscape of PNH and its potential co-occurrence with other genetic syndromes.
- Further research into this specific deletion may elucidate new genotype-phenotype correlations and therapeutic targets for PNH and related neurodevelopmental disorders.
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