title: Association between a novel mutation in SLC20A2 and familial idiopathic basal ganglia calcification.
abstract: Familial idiopathic basal ganglia calcification (FIBGC) is a rare, autosomal dominant disorder involving bilateral calcification of the basal ganglia. To identify gene mutations related to a Chinese FIBGC lineage, we evaluated available individuals in the family using CT scans. DNA was extracted from the peripheral blood of available family members, and both exonic and flanking intronic sequences of the SLC20A2 gene were amplified by PCR and then sequenced. Non-denaturing polyacrylamide gel electrophoresis (PAGE) was used to confirm the presence of mutations. Allele imbalances of the SLC20A2 gene or relative quantity of SLC20A2 transcripts were evaluated using qRT-PCR. A novel heterozygous single base-pair deletion (c.510delA) within the SLC20A2 gene was identified. This deletion mutation was found to co-segregate with basal ganglia calcification in all of the affected family members but was not detected in unaffected individuals or in 167 unrelated Han Chinese controls. The mutation will cause a frameshift, producing a truncated SLC20A2 protein with a premature termination codon, most likely leading to the complete loss of function of the SLC20A2 protein. This mutation may also lead to a reduction in SLC20A2 mRNA expression by approximately 30% in cells from affected individuals. In conclusion, we identified a novel mutation in SLC20A2 that is linked to FIBGC. In addition to the loss of function at the protein level, decreasing the expression of SLC20A2 mRNA may be another mechanism that can regulate SLC20A2 function in IBGC individuals. We propose that the regional expression pattern of SLC20A1 and SLC20A2 might explain the unique calcification pattern observed in FIBGC patients.
authors: Research Center for Medical Genomics, Key Laboratory of Medical Cell Biology, Ministry of Education, College of Basic Medical Science, China Medical University, Shenyang, China.
authors: Yang
authors: Y
authors: Zhang
authors: Xianan
authors: X
authors: Guo
authors: Anhua
authors: A
authors: Wu
mesh_terms: D000293:Adolescent; D000328:Adult; D000483:Alleles; D001480:Basal Ganglia Diseases / Q000175:diagnosis / Q000235:genetics*; D001483:Base Sequence; D001921:Brain / Q000473:pathology; D002114:Calcinosis / Q000175:diagnosis / Q000235:genetics*; D002648:Child; D002675:Child, Preschool; D005260:Female; D056726:Genetic Association Studies; D006801:Humans; D008297:Male; D008875:Middle Aged; D009154:Mutation; D019636:Neurodegenerative Diseases / Q000175:diagnosis / Q000235:genetics*; D010375:Pedigree; D050611:Sodium-Phosphate Cotransporter Proteins, Type III / Q000235:genetics*; D014057:Tomography, X-Ray Computed; D014158:Transcription, Genetic; D055815:Young Adult
chemical_list: C493589:SLC20A2 protein, human; D050611:Sodium-Phosphate Cotransporter Proteins, Type III