A diagnostic gene chip for hereditary spastic paraplegias

• The HSP gene-chip consists of ninety-six hot point mutations.
• We have used this diagnostic gene chip to detect ninety-six HSP patients.
• The call rate of the diagnostic gene chip is 97.7% and the consistency is 99.0%.
• We genetically diagnosed a HSP patient with a c.316G>C substitution in SPG6.
• The HSP gene-chip is a useful technique for preliminary screening of this disease.

Hereditary spastic paraplegias (HSPs) are a group of clinically and genetically heterogeneous monogenic neurodegenerative disorders. The gene screen of hereditary spastic paraplegias patients remains time consuming and costly because of their highly heterogeneous. As we know, there are some hot spots of mutation in many genes causing HSPs. Our aim was to develop a quick method for gene screen of HSP patients. The online mutation data banks of HSPs were searched and Chinese data for point mutations were mainly considered. Then mutations were comprehensively analyzed and ninety-six more common point mutations of HSPs disease genes were chose for the 96-plex GoldenGate assay diagnostic gene chip for HSPs. After that, we used this diagnostic gene chip to detect ninety-six clinically diagnosed HSP patients. For validation purpose, six previously Sanger sequenced cases with known point mutations were redetected on this array. The scores of all the ninety-six point mutations were between 0.601 and 0.993, and the call rate of the whole gene chip was 97.7% and its consistency was 99.0%. A patient suspected with a c.316G>C substitution in SPG6 was detected by the chip, which was further confirmed by polymerase chain reaction and sequencing. The high successful performance of this GoldenGate assay makes it a useful technique for preliminary genetic screening for HSP patients and it may be used in clinic in the future.