1. van Dijk, E. L., Auger, H., Jaszczyszyn, Y. & Thermes, C. T. Ten years of next-generation sequencing technology. Trends Genet. 30,
418–426. https://doi.org/10.1016/j.tig.2014.07.001 (2014).
2. Plagnol, V. et al. A robust model for read count data in exome sequencing experiments and implications for copy number variant
calling. Bioinformatics 28, 2747–2754. https://doi.org/10.1093/bioinformatics/bts526 (2012).
3. Zare, F., Dow, M., Monteleone, N., Hosny, A. & Nabavi, S. An evaluation of copy number variation detection tools for cancer using
whole exome sequencing data. BMC Bioinform. 18, 286. https://doi.org/10.1186/s12859-017-1705-x (2017).
4. Bis, D. M. et al. Uniparental disomy determined by whole-exome sequencing in a spectrum of rare motoneuron diseases and
ataxias. Mol. Genet. Genomic Med. 5, 280–286. https://doi.org/10.1002/mgg3.285 (2017).
5. Markello, T. C. et al. Vascular pathology of medial arterial calcifications in NT5E deficiency: Implications for the role of adenosine
in pseudoxanthoma elasticum. Mol. Genet. Metab. 103, 44–50. https://doi.org/10.1016/j.ymgme.2011.01.018 (2011).
6. Taruscio, D. et al. Undiagnosed diseases network international (UDNI): White paper for global actions to meet patient needs. Mol.
Genet. Metab. 116, 223–225. https://doi.org/10.1016/j.ymgme.2015.11.003 (2015).
7. Beaulieu, C. L. et al. FORGE Canada Consortium: Outcomes of a 2-year national rare-disease gene-discovery project. Am. J. Hum.
Genet. 94, 809–817. https://doi.org/10.1016/j.ajhg.2014.05.003 (2014).
Scientific Reports |
Vol:.(1234567890)
(2022) 12:14589 |
https://doi.org/10.1038/s41598-022-14161-6
www.nature.com/scientificreports/
8. Firth, H. V., Wright, C. F., DDD Study. The deciphering developmental disorders (DDD) study. Dev. Med. Child Neurol. 53, 702–703.
https://doi.org/10.1111/j.1469-8749.2011.04032.x (2011).
9. Adachi, T. et al. Japan’s initiative on rare and undiagnosed diseases (IRUD): Towards an end to the diagnostic odyssey. Eur. J. Hum.
Genet. 25, 1025–1028. https://doi.org/10.1038/ejhg.2017.106 (2017).
10. Koboldt, D. C. et al. VarScan 2: Somatic mutation and copy number alteration discovery in cancer by exome sequencing. Genome
Res. 22, 568–576. https://doi.org/10.1101/gr.129684.111 (2012).
11. Wang, K., Li, M. & Hakonarson, H. ANNOVAR: Functional annotation of genetic variants from high-throughput sequencing data.
Nucleic Acids Res. 38, e164. https://doi.org/10.1093/nar/gkq603 (2010).
12. Richards, S. et al. Standards and guidelines for the interpretation of sequence variants: A joint consensus recommendation of the
American College of Medical Genetics and Genomics and the Association for Molecular Pathology. Genet. Med. 17, 405–424.
https://doi.org/10.1038/gim.2015.30 (2015).
13. Sakaguchi, H. et al. Exome sequencing identifies secondary mutations of SETBP1 and JAK3 in juvenile myelomonocytic leukemia.
Nat. Genet. 45, 937–941. https://doi.org/10.1038/ng.2698 (2013).
14. Thorvaldsdóttir, H., Robinson, J. T. & Mesirov, J. P. Integrative Genomics Viewer (IGV): High-performance genomics data visualization and exploration. Brief. Bioinform. 14, 178–192. https://doi.org/10.1093/bib/bbs017 (2013).
15. Riggs, E. R. et al. Technical standards for the interpretation and reporting of constitutional copy-number variants: A joint consensus recommendation of the American College of Medical Genetics and Genomics (ACMG) and the Clinical Genome Resource
(ClinGen). Genet. Med. 22, 245–257. https://doi.org/10.1038/s41436-019-0686-8 (2020).
16. Magi, A. et al. H3M2: Detection of runs of homozygosity from whole-exome sequencing data. Bioinformatics 30, 2852–2859.
https://doi.org/10.1093/bioinformatics/btu401 (2014).
17. Green, R. C. et al. ACMG recommendations for reporting of incidental findings in clinical exome and genome sequencing. Genet.
Med. 15, 565–574. https://doi.org/10.1038/gim.2013.73 (2013).
18. Grasberger, H., De Deken, X., Miot, F., Pohlenz, J. & Refetoff, S. Missense mutations of dual oxidase 2 (DUOX2) implicated in
congenital hypothyroidism have impaired trafficking in cells reconstituted with DUOX2 maturation factor. Mol. Endocrinol. 21,
1408–1421. https://doi.org/10.1210/me.2007-0018 (2007).
19. Yamamoto-Shimojima, K. et al. Elucidation of the pathogenic mechanism and potential treatment strategy for a female patient
with spastic paraplegia derived from a single-nucleotide deletion in PLP1. J. Hum. Genet. 64, 665–671. https://doi.org/10.1038/
s10038-019-0600-x (2019).
20. Kawaguchi, M. et al. Novel biallelic FA2H mutations in a Japanese boy with fatty acid hydroxylase-associated neurodegeneration.
Brain Dev. 42, 217–221. https://doi.org/10.1016/j.braindev.2019.11.006,Pubmed:31837835 (2020).
21. Nakamura, Y. et al. A novel CUL4B splice site variant in a young male exhibiting less pronounced features. Hum. Genome Var. 6,
43. https://doi.org/10.1038/s41439-019-0074-6 (2019).
22. Nakamura, Y. et al. Biallelic mutations in SZT2 cause a discernible clinical entity with epilepsy, developmental delay, macrocephaly
and a dysmorphic corpus callosum. Brain Dev. 40, 134–139. https://doi.org/10.1016/j.braindev.2017.08.003 (2018).
23. Yang, Y. et al. Molecular findings among patients referred for clinical whole-exome sequencing. JAMA 312, 1870–1879. https://
doi.org/10.1001/jama.2014.14601 (2014).
24. Gahl, W. A. et al. The National Institutes of Health Undiagnosed Diseases Program: Insights into rare diseases. Genet. Med. 14,
51–59. https://doi.org/10.1038/gim.0b013e318232a005 (2012).
25. Splinter, K. et al. Effect of genetic diagnosis on patients with previously undiagnosed disease. N. Engl. J. Med. 379, 2131–2139.
https://doi.org/10.1056/NEJMoa1714458 (2018).
26. Lee, H. et al. Clinical exome sequencing for genetic identification of rare Mendelian disorders. JAMA 312, 1880–1887. https://doi.
org/10.1001/jama.2014.14604 (2014).
27. Grasberger, H. & Refetoff, S. Genetic causes of congenital hypothyroidism due to dyshormonogenesis. Curr. Opin. Pediatr. 23,
421–428. https://doi.org/10.1097/MOP.0b013e32834726a4 (2011).
28. Paprocka, J. et al. Angelman syndrome and hypothyroidism—Coincidence or unique correlation?. Neuro Endocrinol. Lett. 28,
545–546 (2007).
29. Monterrubio-Ledezma, C. E., Bobadilla-Morales, L., Pimentel-Gutiérrez, H. J., Corona-Rivera, J. R. & Corona-Rivera, A. Angelman syndrome and thyroid dysfunction. Genet. Couns. 23, 353–357 (2012).
30. Del Gaudio, D. et al. Diagnostic testing for uniparental disomy: a points to consider statement from the American College of
Medical Genetics and Genomics (ACMG). Genet. Med. 22, 1133–1141. https://d
oi.o
rg/1 0.1 038/s 41436-0 20-0 782-9 ,Pubmed:3 2296
163 (2020).
Acknowledgements
The authors would like to thank all clinicians, patients, and their families. The authors would also like to thank
Ms. Yoshie Miura and Ms. Hiroko Ono for their valuable assistance. The authors acknowledge the Division for
Medical Research Engineering, Nagoya University Graduate School of Medicine for technical support and the
Human Genome Center, Institute of Medical Science, the University of Tokyo (https://sc.hgc.jp/shirokane.html)
for providing super-computing resources. This work was supported by grants from the Japan Agency for Medical
Research and Development (Grant nos. JP17ek0109151 and JP20ek0109301). The authors would like to thank
Enago (https://www.enago.jp) for the English language review.
Author contributions
K.N. and S.N. performed the research, analyzed the data, and wrote the paper. H.M. and Y.Na. designed and
performed the research, led the project, and wrote the paper. Y.O., K.S., M.H., N.Y., A.Su., Y.Ni., A.Sh., A.Y.,
Y.Ts., F.S., M.K., M.W., S.Ka., and K.K. performed the research and analyzed the data. H.A., T.Ku., Y.M., H.K.,
J.N., and S.M. collected specimens and performed the research. T.N., H.I., N.I., T.Y., A.O., T.O., S. Ko., T. Ka.,
T.H., S.S., and Y.Ta. designed the research and analyzed the data.
Competing interests The authors declare no competing interests.
Additional information
Supplementary Information The online version contains supplementary material available at https://doi.org/
10.1038/s41598-022-14161-6.
Correspondence and requests for materials should be addressed to S.S. or Y.T.
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