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  Mutations in the alpha 1,2-mannosidase gene, MAN1B1, cause autosomal-recessive intellectual disability

Rafiq, M. A., Kuss, A. W., Puettmann, L., Noor, A., Ramiah, A., Ali, G., et al. (2011). Mutations in the alpha 1,2-mannosidase gene, MAN1B1, cause autosomal-recessive intellectual disability. Am J Hum Genet, 89(1), 176-82. Retrieved from http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&dopt=Citation&list_uids=21763484 http://pdn.sciencedirect.com/science?_ob=MiamiImageURL&_cid=276895&_user=28761&_pii=S000292971100259X&_check=y&_origin=article&_zone=toolbar&_coverDate=15-Jul-2011&view=c&originContentFamily=serial&wchp=dGLbVBA-zSkzk&md5=0eb2e52649f898aa8cfb27ed4aec6136/1-s2.0-S000292971100259X-main.pdf.

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Item Permalink: http://hdl.handle.net/11858/00-001M-0000-0010-797C-3 Version Permalink: http://hdl.handle.net/11858/00-001M-0000-0010-797D-1
Genre: Journal Article

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Rafiq, M. A., Author
Kuss, A. W.1, Author              
Puettmann, L.1, Author              
Noor, A., Author
Ramiah, A., Author
Ali, G., Author
Hu, H.2, Author              
Kerio, N. A., Author
Xiang, Y., Author
Garshasbi, M.2, Author              
Khan, M. A., Author
Ishak, G. E., Author
Weksberg, R., Author
Ullmann, R.3, Author              
Tzschach, A.2, Author              
Kahrizi, K., Author
Mahmood, K., Author
Naeem, F., Author
Ayub, M., Author
Moremen, K. W., Author
Vincent, J. B., AuthorRopers, H. H.2, Author              Ansar, M., AuthorNajmabadi, H., Author more..
Affiliations:
1Familial Cognitive Disorders (Luciana Musante), Dept. of Human Molecular Genetics (Head: Hans-Hilger Ropers), Max Planck Institute for Molecular Genetics, Max Planck Society, ou_1479644              
2Dept. of Human Molecular Genetics (Head: Hans-Hilger Ropers), Max Planck Institute for Molecular Genetics, Max Planck Society, ou_1433549              
3Molecular Cytogenetics (Reinhard Ullmann), Dept. of Human Molecular Genetics (Head: Hans-Hilger Ropers), Max Planck Institute for Molecular Genetics, Max Planck Society, ou_1479645              

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Free keywords: Adolescent; Adult; Amino Acid Sequence; Asian Continental Ancestry Group/genetics; Child; Chromosomes, Human, Pair 9; Consanguinity; Female; *Genes, Recessive; Genetic Linkage; Genome-Wide Association Study/methods; Homozygote; Humans; Intellectual Disability/*genetics; Iran; Male; Mannosidases/*genetics/metabolism; Membrane Proteins/*genetics/metabolism; Molecular Sequence Data; *Mutation, Missense; Pakistan; Pedigree; Polymorphism, Single Nucleotide; Protein Structure, Tertiary; Young Adult
 Abstract: We have used genome-wide genotyping to identify an overlapping homozygosity-by-descent locus on chromosome 9q34.3 (MRT15) in four consanguineous families affected by nonsyndromic autosomal-recessive intellectual disability (NS-ARID) and one in which the patients show additional clinical features. Four of the families are from Pakistan, and one is from Iran. Using a combination of next-generation sequencing and Sanger sequencing, we have identified mutations in the gene MAN1B1, encoding a mannosyl oligosaccharide, alpha 1,2-mannosidase. In one Pakistani family, MR43, a homozygous nonsense mutation (RefSeq number NM_016219.3: c.1418G>A [p.Trp473*]), segregated with intellectual disability and additional dysmorphic features. We also identified the missense mutation c. 1189G>A (p.Glu397Lys; RefSeq number NM_016219.3), which segregates with NS-ARID in three families who come from the same village and probably have shared inheritance. In the Iranian family, the missense mutation c.1000C>T (p.Arg334Cys; RefSeq number NM_016219.3) also segregates with NS-ARID. Both missense mutations are at amino acid residues that are conserved across the animal kingdom, and they either reduce k(cat) by approximately 1300-fold or disrupt stable protein expression in mammalian cells. MAN1B1 is one of the few NS-ARID genes with an elevated mutation frequency in patients with NS-ARID from different populations.

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Title: Am J Hum Genet
Source Genre: Journal
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Pages: - Volume / Issue: 89 (1) Sequence Number: - Start / End Page: 176 - 82 Identifier: ISSN: 1537-6605 (Electronic) 0002-9297 (Linking)