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Identification of two novel critical mutations in PCNT gene resulting in microcephalic osteodysplastic primordial dwarfism type II associated with multiple intracranial aneurysms.

Abstract

Microcephalic osteodysplastic primordial dwarfism type II (MOPD II) is a highly detrimental human autosomal inherited recessive disorder. The hallmark characteristics of this disease are intrauterine and postnatal growth restrictions, with some patients also having cerebrovascular problems such as cerebral aneurysms. The genomic basis behind most clinical features of MOPD II remains largely unclear. The aim of this work was to identify the genetic defects in a Chinese family with MOPD II associated with multiple intracranial aneurysms. The patient had typical MOPD II syndrome, with subarachnoid hemorrhage and multiple intracranial aneurysms. We identified three novel mutations in the PCNT gene, including one single base alteration (9842A>C in exon 45) and two deletions (Del-C in exon 30 and Del-16 in exon 41). The deletions were co-segregated with the affected individual in the family and were not present in the control population. Computer modeling demonstrated that the deletions may cause drastic changes on the secondary and tertiary structures, affecting the hydrophilicity and hydrophobicity of the mutant proteins. In conclusion, we identified two novel mutations in the PCNT gene associated with MOPD II and intracranial aneurysms, and the mutations were expected to alter the stability and functioning of the protein by computer modeling.

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  • Authors+Show Affiliations

    ,

    Genomics Research Center (One of the State-Province Key Laboratory of Biopharmaceutical Engineering, China), Harbin Medical University, Harbin, China.

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    Department of Neurology, The First Affiliated Hospital, Harbin Medical University, Harbin, China.

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    Department of Neurosurgery, The First Affiliated Hospital, Harbin Medical University, Harbin, China.

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    Department of Antibiotics, Heilongjiang Province Food and Drug Inspection Testing Institute, Harbin, China.

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    Department of Antibiotics, Heilongjiang Province Food and Drug Inspection Testing Institute, Harbin, China.

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    Department of Neurology, Daqing Oilfield General Hospital, 35 ward, Daqing, China.

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    Department of Neurology, The First Affiliated Hospital, Harbin Medical University, Harbin, China. fenghonglin5678@sina.com.

    ,

    Department of Neurosurgery, The First Affiliated Hospital, Harbin Medical University, Harbin, China. Linzhiguo2009@sohu.com.

    Genomics Research Center (One of the State-Province Key Laboratory of Biopharmaceutical Engineering, China), Harbin Medical University, Harbin, China. slliu@ucalgary.ca. Department of Microbiology, Immunology and Infectious Diseases, University of Calgary, Calgary, Canada. slliu@ucalgary.ca.

    Source

    Metabolic brain disease 30:6 2015 Dec pg 1387-94

    MeSH

    Adolescent
    Adult
    Amino Acid Sequence
    Antigens
    Asian Continental Ancestry Group
    Child
    Computer Simulation
    Dwarfism
    Female
    Fetal Growth Retardation
    Gene Deletion
    Growth Disorders
    Humans
    Hydrophobic and Hydrophilic Interactions
    Intracranial Aneurysm
    Male
    Microcephaly
    Models, Molecular
    Molecular Sequence Data
    Mutation
    Osteochondrodysplasias
    Pedigree
    Protein Structure, Secondary
    Protein Structure, Tertiary
    Subarachnoid Hemorrhage

    Pub Type(s)

    Case Reports
    Journal Article
    Research Support, Non-U.S. Gov't

    Language

    eng

    PubMed ID

    26231886

    Citation

    Li, Fei-Feng, et al. "Identification of Two Novel Critical Mutations in PCNT Gene Resulting in Microcephalic Osteodysplastic Primordial Dwarfism Type II Associated With Multiple Intracranial Aneurysms." Metabolic Brain Disease, vol. 30, no. 6, 2015, pp. 1387-94.
    Li FF, Wang XD, Zhu MW, et al. Identification of two novel critical mutations in PCNT gene resulting in microcephalic osteodysplastic primordial dwarfism type II associated with multiple intracranial aneurysms. Metab Brain Dis. 2015;30(6):1387-94.
    Li, F. F., Wang, X. D., Zhu, M. W., Lou, Z. H., Zhang, Q., Zhu, C. Y., ... Liu, S. L. (2015). Identification of two novel critical mutations in PCNT gene resulting in microcephalic osteodysplastic primordial dwarfism type II associated with multiple intracranial aneurysms. Metabolic Brain Disease, 30(6), pp. 1387-94. doi:10.1007/s11011-015-9712-y.
    Li FF, et al. Identification of Two Novel Critical Mutations in PCNT Gene Resulting in Microcephalic Osteodysplastic Primordial Dwarfism Type II Associated With Multiple Intracranial Aneurysms. Metab Brain Dis. 2015;30(6):1387-94. PubMed PMID: 26231886.
    * Article titles in AMA citation format should be in sentence-case
    TY - JOUR T1 - Identification of two novel critical mutations in PCNT gene resulting in microcephalic osteodysplastic primordial dwarfism type II associated with multiple intracranial aneurysms. AU - Li,Fei-Feng, AU - Wang,Xu-Dong, AU - Zhu,Min-Wei, AU - Lou,Zhi-Hong, AU - Zhang,Qiong, AU - Zhu,Chun-Yu, AU - Feng,Hong-Lin, AU - Lin,Zhi-Guo, AU - Liu,Shu-Lin, Y1 - 2015/08/01/ PY - 2015/04/26/received PY - 2015/07/15/accepted PY - 2015/8/2/entrez PY - 2015/8/2/pubmed PY - 2016/8/24/medline KW - Critical genetic mutations KW - Microcephalic osteodysplastic primordial dwarfism type II KW - Moyamoya disease KW - Multiple intracranial aneurysms KW - PCNT SP - 1387 EP - 94 JF - Metabolic brain disease JO - Metab Brain Dis VL - 30 IS - 6 N2 - Microcephalic osteodysplastic primordial dwarfism type II (MOPD II) is a highly detrimental human autosomal inherited recessive disorder. The hallmark characteristics of this disease are intrauterine and postnatal growth restrictions, with some patients also having cerebrovascular problems such as cerebral aneurysms. The genomic basis behind most clinical features of MOPD II remains largely unclear. The aim of this work was to identify the genetic defects in a Chinese family with MOPD II associated with multiple intracranial aneurysms. The patient had typical MOPD II syndrome, with subarachnoid hemorrhage and multiple intracranial aneurysms. We identified three novel mutations in the PCNT gene, including one single base alteration (9842A>C in exon 45) and two deletions (Del-C in exon 30 and Del-16 in exon 41). The deletions were co-segregated with the affected individual in the family and were not present in the control population. Computer modeling demonstrated that the deletions may cause drastic changes on the secondary and tertiary structures, affecting the hydrophilicity and hydrophobicity of the mutant proteins. In conclusion, we identified two novel mutations in the PCNT gene associated with MOPD II and intracranial aneurysms, and the mutations were expected to alter the stability and functioning of the protein by computer modeling. SN - 1573-7365 UR - https://www.unboundmedicine.com/medline/citation/26231886/Identification_of_two_novel_critical_mutations_in_PCNT_gene_resulting_in_microcephalic_osteodysplastic_primordial_dwarfism_type_II_associated_with_multiple_intracranial_aneurysms_ L2 - https://doi.org/10.1007/s11011-015-9712-y DB - PRIME DP - Unbound Medicine ER -