Medizinische Universität Graz Austria/Österreich - Forschungsportal - Medical University of Graz
Gewählte Publikation:
SHR Neuro Krebs Kardio Lipid Stoffw Microb
Bhat, V; Girimaji, SC; Mohan, G; Arvinda, HR; Singhmar, P; Duvvari, MR; Kumar, A.
Mutations in WDR62, encoding a centrosomal and nuclear protein, in Indian primary microcephaly families with cortical malformations.
Clin Genet. 2011; 80(6): 532-540.
Doi: 10.1111/j.1399-0004.2011.01686.x
Web of Science
PubMed
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- Führende Autor*innen der Med Uni Graz
- Bhat Kumble Vishwanath
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- Abstract:
- Primary microcephaly is an autosomal recessive disorder characterized by smaller than normal brain size and mental retardation. It is genetically heterogeneous with seven loci: MCPH1-MCPH7. We have previously reported genetic analysis of 35 families, including the identification of the MCPH7 gene STIL. Of the 35 families, three families showed linkage to the MCPH2 locus. Recent whole-exome sequencing studies have shown that the WDR62 gene, located in the MCPH2 candidate region, is mutated in patients with severe brain malformations. We therefore sequenced the WDR62 gene in our MCPH2 families and identified two novel homozygous protein truncating mutations in two families. Affected individuals in the two families had pachygyria, microlissencephaly, band heterotopias, gyral thickening, and dysplastic cortex. Using immunofluorescence study, we showed that, as with other MCPH proteins, WDR62 localizes to centrosomes in A549, HepG2, and HaCaT cells. In addition, WDR62 was also localized to nucleoli. Bioinformatics analysis predicted two overlapping nuclear localization signals and multiple WD-40 repeats in WDR62. Two other groups have also recently identified WDR62 mutations in MCPH2 families. Our results therefore add further evidence that WDR62 is the MCPH2 gene. The present findings will be helpful in genetic diagnosis of patients linked to the MCPH2 locus. © 2011 John Wiley & Sons A/S.
- Find related publications in this database (using NLM MeSH Indexing)
- Biological Markers -
- Brain - metabolism Brain - pathology
- Cell Line, Tumor -
- Cell Nucleus - genetics Cell Nucleus - metabolism
- Centrosome - metabolism
- Child -
- Child, Preschool -
- Computational Biology -
- DNA Mutational Analysis -
- Exome -
- Female -
- Fluorescent Antibody Technique -
- Genetic Linkage -
- Genotype -
- Hep G2 Cells -
- Humans -
- Humans - epidemiology
- Lissencephaly - diagnosis Lissencephaly - genetics Lissencephaly - pathology
- Magnetic Resonance Imaging -
- Male -
- Microcephaly - epidemiology Microcephaly - genetics Microcephaly - pathology
- Mutation, Missense -
- Nerve Tissue Proteins - genetics Nerve Tissue Proteins - metabolism
- Pedigree -
- Find related publications in this database (Keywords)
- centrosome
- cortical malformations
- Indian families
- MCPH
- MCPH2
- WDR62