title: 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.
authors.affiliation: Genomics Research Center (One of the State-Province Key Laboratory of Biopharmaceutical Engineering, China), Harbin Medical University, Harbin, China.
authors.forename: Fei-Feng
authors.initials: FF
authors.lastname: Li
authors.affiliation: Department of Neurology, The First Affiliated Hospital, Harbin Medical University, Harbin, China.
authors.forename: Xu-Dong
authors.initials: XD
authors.lastname: Wang
authors.affiliation: Department of Neurosurgery, The First Affiliated Hospital, Harbin Medical University, Harbin, China.
authors.forename: Min-Wei
authors.initials: MW
authors.lastname: Zhu
authors.affiliation: Department of Antibiotics, Heilongjiang Province Food and Drug Inspection Testing Institute, Harbin, China.
authors.forename: Zhi-Hong
authors.initials: ZH
authors.lastname: Lou
authors.affiliation: Department of Antibiotics, Heilongjiang Province Food and Drug Inspection Testing Institute, Harbin, China.
authors.forename: Qiong
authors.initials: Q
authors.lastname: Zhang
authors.affiliation: Department of Neurology, Daqing Oilfield General Hospital, 35 ward, Daqing, China.
authors.forename: Chun-Yu
authors.initials: CY
authors.lastname: Zhu
authors.affiliation: Department of Neurology, The First Affiliated Hospital, Harbin Medical University, Harbin, China. fenghonglin5678@sina.com.
authors.forename: Hong-Lin
authors.initials: HL
authors.lastname: Feng
authors.affiliation: Department of Neurosurgery, The First Affiliated Hospital, Harbin Medical University, Harbin, China. Linzhiguo2009@sohu.com.
authors.forename: Zhi-Guo
authors.initials: ZG
authors.lastname: Lin
authors.affiliation: 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.
authors.forename: Shu-Lin
authors.initials: SL
authors.lastname: Liu
mesh_terms: D000293:Adolescent; D000328:Adult; D000595:Amino Acid Sequence; D000941:Antigens / Q000737:chemistry / Q000235:genetics*; D044466:Asian People; D002648:Child; D003198:Computer Simulation; D004392:Dwarfism / Q000150:complications / Q000235:genetics*; D005260:Female; D005317:Fetal Growth Retardation / Q000209:etiology / Q000235:genetics*; D017353:Gene Deletion; D006130:Growth Disorders / Q000209:etiology / Q000235:genetics; D006801:Humans; D057927:Hydrophobic and Hydrophilic Interactions; D002532:Intracranial Aneurysm / Q000209:etiology / Q000235:genetics*; D008297:Male; D008831:Microcephaly / Q000150:complications / Q000235:genetics*; D008958:Models, Molecular; D008969:Molecular Sequence Data; D009154:Mutation / Q000235:genetics*; D010009:Osteochondrodysplasias / Q000150:complications / Q000235:genetics*; D010375:Pedigree; D017433:Protein Structure, Secondary; D017434:Protein Structure, Tertiary; D013345:Subarachnoid Hemorrhage / Q000150:complications / Q000235:genetics
chemical_list: D000941:Antigens; C086178:pericentrin
keywords: Critical genetic mutations; Microcephalic osteodysplastic primordial dwarfism type II; Moyamoya disease; Multiple intracranial aneurysms; PCNT