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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.
Metab Brain Dis. 2015 Dec; 30(6):1387-94.MB

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

Li FF
Genomics Research Center (One of the State-Province Key Laboratory of Biopharmaceutical Engineering, China), Harbin Medical University, Harbin, China.
Wang XD
Department of Neurology, The First Affiliated Hospital, Harbin Medical University, Harbin, China.
Zhu MW
Department of Neurosurgery, The First Affiliated Hospital, Harbin Medical University, Harbin, China.
Lou ZH
Department of Antibiotics, Heilongjiang Province Food and Drug Inspection Testing Institute, Harbin, China.
Zhang Q
Department of Antibiotics, Heilongjiang Province Food and Drug Inspection Testing Institute, Harbin, China.
Zhu CY
Department of Neurology, Daqing Oilfield General Hospital, 35 ward, Daqing, China.
Feng HL
Department of Neurology, The First Affiliated Hospital, Harbin Medical University, Harbin, China. fenghonglin5678@sina.com.
Lin ZG
Department of Neurosurgery, The First Affiliated Hospital, Harbin Medical University, Harbin, China. Linzhiguo2009@sohu.com.
Liu SL
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.

MeSH

AdolescentAdultAmino Acid SequenceAntigensAsian Continental Ancestry GroupChildComputer SimulationDwarfismFemaleFetal Growth RetardationGene DeletionGrowth DisordersHumansHydrophobic and Hydrophilic InteractionsIntracranial AneurysmMaleMicrocephalyModels, MolecularMolecular Sequence DataMutationOsteochondrodysplasiasPedigreeProtein Structure, SecondaryProtein Structure, TertiarySubarachnoid 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., Feng, H. L., Lin, Z. G., & 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), 1387-94. https://doi.org/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 -