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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Acknowledgements
The authors thank the patient, the family members and other subjects for their cooperation and participation in this study. This work was supported by a grant from the Heilongjiang Provincial Educational Department (12541431). The funder had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.
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The authors have declared that no competing interests exist.
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Study concept or design: FFL, SLL; specimen collection: XDW, MWZ, HLF, ZGL, CYZ; carry out the experiment: FFL, ZHL, QZ; data analysis: FFL, SLL; clinical diagnosis: XDW, MWZ, HLF, ZGL, CYZ; funding: FFL, SLL; drafting/revising of manuscript: FFL, SLL. All authors read and approved the final manuscript.
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Fei-Feng Li, Xu-Dong Wang and Min-Wei Zhu contributed equally to this work.
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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 30, 1387–1394 (2015). https://doi.org/10.1007/s11011-015-9712-y
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DOI: https://doi.org/10.1007/s11011-015-9712-y