Mutations in FLVCR2 Are Associated with Proliferative Vasculopathy and Hydranencephaly-Hydrocephaly Syndrome (Fowler Syndrome)
| Autor: | Tamás Marton, Christopher J. Ricketts, Richard C. Trembath, Catherine Fallet-Bianco, Fatimah Rahman, M. T. Yacoubi, Phillip Cox, Mark R. Morris, Esther Meyer, Louise J. Tee, Mudher Al-Adnani, Bettina Bessières, Neil V. Morgan, Shanaz Pasha, David Tannahill, Denise Williams, Anne Bazin, Pierre Dechelotte, Eamonn R. Maher |
|---|---|
| Rok vydání: | 2010 |
| Předmět: |
Male
Models Molecular Candidate gene Hydranencephaly Consanguinity Mice 0302 clinical medicine Pregnancy Genetics(clinical) Conserved Sequence Genetics (clinical) Oligonucleotide Array Sequence Analysis Genetics 0303 health sciences Fowler syndrome Syndrome Phenotype Pedigree 3. Good health medicine.anatomical_structure Receptors Virus Female Hydrocephalus Molecular Sequence Data Central nervous system Genes Recessive Biology Polymorphism Single Nucleotide 03 medical and health sciences Germline mutation Report medicine Animals Humans SNP Abnormalities Multiple Amino Acid Sequence Vascular Diseases Germ-Line Mutation 030304 developmental biology Chromosomes Human Pair 14 Base Sequence Sequence Homology Amino Acid Membrane Transport Proteins Chromosome DNA medicine.disease Protein Structure Tertiary Amino Acid Substitution 030217 neurology & neurosurgery |
| Zdroj: | The American Journal of Human Genetics. 86:471-478 |
| ISSN: | 0002-9297 |
| DOI: | 10.1016/j.ajhg.2010.02.004 |
| Popis: | Proliferative vasculopathy and hydranencephaly-hydrocephaly syndrome (PVHH), also known as Fowler syndrome, is an autosomal-recessively inherited prenatal lethal disorder characterized by hydranencephaly; brain stem, basal ganglia, and spinal cord diffuse clastic ischemic lesions with calcifications; glomeruloid vasculopathy of the central nervous system and retinal vessels; and a fetal akinesia deformation sequence (FADS) with muscular neurogenic atrophy. To identify the molecular basis for Fowler syndrome, we performed autozygosity mapping studies in three consanguineous families. The results of SNP microarrays and microsatellite marker genotyping demonstrated linkage to chromosome 14q24.3. Direct sequencing of candidate genes within the target interval revealed five different germline mutations in FLVCR2 in five families with Fowler syndrome. FLVCR2 encodes a transmembrane transporter of the major facilitator superfamily (MFS) hypothesized to be involved in regulation of growth, calcium exchange, and homeostasis. This is the first gene to be associated with Fowler syndrome, and this finding provides a basis for further studies to elucidate the pathogenetic mechanisms and phenotypic spectrum of associated disorders. |
| Databáze: | OpenAIRE |
| Externí odkaz: |
|