Phenotype categorization of neurofibromatosis type I and correlation to NF1 mutation types

Eungu Kang, Yoon Myung Kim, Go Hun Seo, Arum Oh, Hee Mang Yoon, Young Shin Ra, Eun Key Kim, Heyry Kim, Sun Hee Heo, Gu Hwan Kim, Mark J. Osborn, Jakub Tolar, Han Wook Yoo, Beom Hee Lee

Research output: Contribution to journalArticlepeer-review

33 Scopus citations


Neurofibromatosis type 1 (NF1) is caused by heterozygous mutation in the NF1 gene. NF1 is one of the most common human genetic diseases. However, the overall genotype–phenotype correlation has not been known, due to a wide spectrum of genotypic and phenotypic heterogeneity. Here we describe the detailed clinical and genetic features of 427 Korean NF1 patients from 389 unrelated families. Long range PCR and sequencing of genomic DNA with multiplex ligation-dependent probe amplification analysis identified 250 different NF1 mutations in 363 families (93%), including 94 novel mutations. With an emphasis on phenotypes requiring medical attention (classified and termed: NF1+), we investigated the correlation of NF1+ and mutation types. NF1+ was more prevalent in patients with truncating/splicing mutations and large deletions than in those with missense mutations (59.6%, 64.3% vs. 36.6%, p = 0.001). This difference was especially significant in the patients younger than age 19 years. The number of items in NF1+ was a higher in the former groups (0.95 ± 0.06, 1.18 ± 0.20 vs. 0.56 ± 0.10, p = 0.002). These results suggest that mutation types are associated not only with higher prevalence of severe phenotypes in NF1 but also with their earlier onset.

Original languageEnglish (US)
Pages (from-to)79-89
Number of pages11
JournalJournal of Human Genetics
Issue number2
StatePublished - Jan 1 2020

Bibliographical note

Funding Information:
Funding This research was supported in part by the Bio & Medical Technology Development Program of the National Research Foundation (NRF) funded by the Korean government (NRF-2015K1A4A3046807 and NRF-2018M3A9H1078335).

Publisher Copyright:
© 2019, The Author(s), under exclusive licence to The Japan Society of Human Genetics.

PubMed: MeSH publication types

  • Journal Article


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