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SHR Neuro Krebs Kardio Lipid Stoffw Microb

Khan, MA; Rupp, VM; Orpinell, M; Hussain, MS; Altmüller, J; Steinmetz, MO; Enzinger, C; Thiele, H; Höhne, W; Nürnberg, G; Baig, SM; Ansar, M; Nürnberg, P; Vincent, JB; Speicher, MR; Gönczy, P; Windpassinger, C.
A missense mutation in the PISA domain of HsSAS-6 causes autosomal recessive primary microcephaly in a large consanguineous Pakistani family.
Hum Mol Genet. 2014; 23(22):5940-5949 Doi: 10.1093/hmg/ddu318 [OPEN ACCESS]
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Führende Autor*innen der Med Uni Graz
Rupp Verena
Windpassinger Christian
Co-Autor*innen der Med Uni Graz
Enzinger Christian
Speicher Michael

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Asymmetric cell division is essential for normal human brain development. Mutations in several genes encoding centrosomal proteins that participate in accurate cell division have been reported to cause autosomal recessive primary microcephaly (MCPH). By homozygosity mapping including three affected individuals from a consanguineous MCPH family from Pakistan, we delineated a critical region of 18.53 Mb on Chromosome 1p21.3-1p13.1. This region contains the gene encoding HsSAS-6, a centrosomal protein primordial for seeding the formation of new centrioles during the cell cycle. Both next-generation and Sanger sequencing revealed a homozygous c.185T>C missense mutation in the HsSAS-6 gene, resulting in a p.Ile62Thr substitution within a highly conserved region of the PISA domain of HsSAS-6. This variant is neither present in any single-nucleotide polymorphism or exome sequencing databases nor in a Pakistani control cohort. Experiments in tissue culture cells revealed that the Ile62Thr mutant of HsSAS-6 is substantially less efficient than the wild-type protein in sustaining centriole formation. Together, our findings demonstrate a dramatic impact of the mutation p.Ile62Thr on HsSAS-6 function and add this component to the list of genes mutated in primary microcephaly. © The Author 2014. Published by Oxford University Press. All rights reserved. For Permissions, please email:
Find related publications in this database (using NLM MeSH Indexing)
Adult -
Amino Acid Sequence -
Asian Continental Ancestry Group - genetics
Base Sequence -
Cell Cycle Proteins - chemistry
Cell Cycle Proteins - genetics
Cell Cycle Proteins - metabolism
Child -
Child, Preschool -
Exome -
Female -
Humans -
Male -
Microcephaly - genetics
Microcephaly - metabolism
Middle Aged -
Molecular Sequence Data -
Mutation, Missense -
Mutation, Missense -
Pedigree -
Polymorphism, Single Nucleotide -
Protein Structure, Tertiary -
Sequence Alignment -

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