Phenotypic and molecular spectrum of Korean patients with Lesch-Nyhan syndrome and attenuated clinical variants
- 59 Downloads
Lesch-Nyhan syndrome (LNS) is an X-linked recessive disorder caused by mutations in the HPRT1 gene. The clinical features and mutation spectrum of 26 Korean LNS patients from 23 unrelated families were retrospectively reviewed. The HPRT1 gene was analyzed by direct sequencing of genomic DNA. The median age at diagnosis was 2.3 years (range, 4 months–22.6 years) and the initial presenting features included developmental delay, orange colored urine, and self-injurious behaviors. Most patients were wheelchair-bound and suffered from urinary complications and neurologic problems such as self-mutilation and developmental delay. Twenty different mutations in HPRT1 were identified among 23 independent pedigrees, including six novel mutations. The most common mutation type was truncating mutations including nonsense and frameshift mutations (45%). Large deletions in the HPRT1 gene were identified in exon 1, exons 5–6, exons 1–9, and at chr X:134,459,540–134,467,241 (7702 bp) including the 5′-untranslated region, exon 1, and a portion of intron 1. In conclusion, this study describes the phenotypic spectrum of LNS and has identified 20 mutations from 23 Korean families, including six novel mutations in Korean patients with LNS.
KeywordsHPRT1 Hypoxanthine guanine phosphoribosyltransferase Hyperuricemia Lesch-Nyhan syndrome
This research was supported by Basic Science Research Program through the National Research Foundation of Korea (NRF) funded by the Ministry of Education (2017R1D1A1B03029638).
Compliance with ethical standards
Conflict of interest
The authors declare no conflicts of interest.
- Ceballos-Picot I, Augé F, Fu R, Olivier-Bandini A, Cahu J, Chabrol B, Aral B, de Martinville B, Lecain JP, Jinnah HA (2013) Phenotypic variation among seven members of one family with deficiency of hypoxanthine-guanine phosphoribosyltransferase. Mol Genet Metab 110:268–274. https://doi.org/10.1016/j.ymgme.2013.08.016 CrossRefGoogle Scholar
- de Gemmis P, Anesi L, Lorenzetto E, Gioachini I, Fortunati E, Zandonà G, Fanin E, Fairbanks L, Andrighetto G, Parmigiani P, Dolcetta D, Nyhan WL, Hladnik U (2010) Analysis of the HPRT1 gene in 35 Italian Lesch-Nyhan families: 45 patients and 77 potential female carriers. Mutat Res 692:1–5. https://doi.org/10.1016/j.mrfmmm.2010.07.003 CrossRefGoogle Scholar
- Fu R, Ceballos-Picot I, Torres RJ, Larovere LE, Yamada Y, Nguyen KV, Hegde M, Visser JE, Schretlen DJ, Nyhan WL, Puig JG, O'Neill PJ, Jinnah HA, Lesch-Nyhan Disease International Study Group (2014a) Genotype-phenotype correlations in neurogenetics: Lesch-Nyhan disease as a model disorder. Brain 137:1282–1303. https://doi.org/10.1093/brain/awt202 CrossRefGoogle Scholar
- Jinnah HA, Ceballos-Picot I, Torres RJ, Visser JE, Schretlen DJ, Verdu A, Larovere LE, Chen CJ, Cossu A, Wu CH, Sampat R, Chang SJ, de Kremer RD, Nyhan W, Harris JC, Reich SG, Puig JG, for the Lesch-Nyhan Disease International Study Group (2010) Attenuated variants of Lesch-Nyhan disease. Brain 133:671–689. https://doi.org/10.1093/brain/awq013 CrossRefGoogle Scholar
- Jurecka A, Popowska E, Tylki-Szymanska A, Kubalska J, Ciara E, Krumina Z, Sykut-Cegielska J, Pronicka E (2008) Hypoxanthine-guanine phosphoribosylotransferase deficiency--the spectrum of polish mutations. J Inherit Metab Dis 31(Suppl 2):S447–S451. https://doi.org/10.1007/s10545-008-1013-8 CrossRefGoogle Scholar
- Kim KJ, Yamada Y, Suzumori K, Choi Y, Yang SW, Cheong HI, Hwang YS, Goto H, Ogasawara N (1997) Molecular analysis of hypoxanthine guanine phosphoribosyltransferase (HPRT) gene in five Korean families with Lesch-Nyhan syndrome. J Korean Med Sci 12:332–339. https://doi.org/10.3346/jkms.1922.214.171.1242 CrossRefGoogle Scholar