Abstract
Opsismodysplasia is an autosomal recessive skeletal disorder characterized by facial dysmorphism, micromelia, platyspondyly and retarded bone maturation. Recently, mutations in the gene encoding inositol polyphosphate phosphatase-like 1 (INPPL1) are found in several families with opsismodysplasia by a homozygosity mapping, followed by whole genome sequencing. We performed an exome sequencing in two unrelated Japanese families with opsismodysplasia and identified a novel INPPL1 mutation, c.1960_1962delGAG, in one family. The mutation is predicted to result in an in-frame deletion (p.E654del) within the central catalytic 5-phosphate domain. Our results further support that INPPL1 is the disease gene for opsismodysplasia and that opsismodysplasia has genetic heterogeneity.
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Acknowledgements
We thank the patients and their family for their help to the study. We also thank the Japanese Skeletal Dysplasia Consortium. This study is supported by research grants from the Ministry of Health, Labor and Welfare (23300101 to SI and NMat.; 23300201 to SI), by Grants-in-Aid for Young Scientists (23689052 to NMiy.) from the Japan Society for the Promotion of Science; by Research on intractable diseases, Health and Labour Sciences Research Grants, H23-Nanchi-Ippan-123 (SI) and by grants from the Japan Science and Technology Agency, the Strategic Research Program for Brain Sciences (11105137 to NMat.), a Grant-in-Aid for Scientific Research on Innovative Areas (Transcription Cycle) from the Ministry of Education, Culture, Sports, Science and Technology of Japan (12024421 to NMat.), a Grant-in-Aid for Scientific Research from the Japan Society for the Promotion of Science (12020465 to NMat.) and the Takeda Science Foundation (to N Miy. and N Mat.). We thank Professors Debora Krakow and Michael Bamshad for their comments on the patients’ phenotypes. We also thank Ms Tomoko Kusadokoro for technical assistance.
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Iida, A., Okamoto, N., Miyake, N. et al. Exome sequencing identifies a novel INPPL1 mutation in opsismodysplasia. J Hum Genet 58, 391–394 (2013). https://doi.org/10.1038/jhg.2013.25
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DOI: https://doi.org/10.1038/jhg.2013.25
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