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 journalArticle

Abstract

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
Volume65
Issue number2
DOIs
StatePublished - Jan 1 2020

Fingerprint

Neurofibromatosis 1
Phenotype
Mutation
Neurofibromatosis 1 Genes
Inborn Genetic Diseases
Sequence Deletion
Multiplex Polymerase Chain Reaction
Medical Genetics
Missense Mutation
DNA Sequence Analysis
Polymerase Chain Reaction

PubMed: MeSH publication types

  • Journal Article

Cite this

Kang, E., Kim, Y. M., Seo, G. H., Oh, A., Yoon, H. M., Ra, Y. S., ... Lee, B. H. (2020). Phenotype categorization of neurofibromatosis type I and correlation to NF1 mutation types. Journal of Human Genetics, 65(2), 79-89. https://doi.org/10.1038/s10038-019-0695-0

Phenotype categorization of neurofibromatosis type I and correlation to NF1 mutation types. / Kang, Eungu; Kim, Yoon Myung; Seo, Go Hun; Oh, Arum; Yoon, Hee Mang; Ra, Young Shin; Kim, Eun Key; Kim, Heyry; Heo, Sun Hee; Kim, Gu Hwan; Osborn, Mark J.; Tolar, Jakub; Yoo, Han Wook; Lee, Beom Hee.

In: Journal of Human Genetics, Vol. 65, No. 2, 01.01.2020, p. 79-89.

Research output: Contribution to journalArticle

Kang, E, Kim, YM, Seo, GH, Oh, A, Yoon, HM, Ra, YS, Kim, EK, Kim, H, Heo, SH, Kim, GH, Osborn, MJ, Tolar, J, Yoo, HW & Lee, BH 2020, 'Phenotype categorization of neurofibromatosis type I and correlation to NF1 mutation types', Journal of Human Genetics, vol. 65, no. 2, pp. 79-89. https://doi.org/10.1038/s10038-019-0695-0
Kang, Eungu ; Kim, Yoon Myung ; Seo, Go Hun ; Oh, Arum ; Yoon, Hee Mang ; Ra, Young Shin ; Kim, Eun Key ; Kim, Heyry ; Heo, Sun Hee ; Kim, Gu Hwan ; Osborn, Mark J. ; Tolar, Jakub ; Yoo, Han Wook ; Lee, Beom Hee. / Phenotype categorization of neurofibromatosis type I and correlation to NF1 mutation types. In: Journal of Human Genetics. 2020 ; Vol. 65, No. 2. pp. 79-89.
@article{94dc0bccff2840049d3793d666ad1c25,
title = "Phenotype categorization of neurofibromatosis type I and correlation to NF1 mutation types",
abstract = "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.",
author = "Eungu Kang and Kim, {Yoon Myung} and Seo, {Go Hun} and Arum Oh and Yoon, {Hee Mang} and Ra, {Young Shin} and Kim, {Eun Key} and Heyry Kim and Heo, {Sun Hee} and Kim, {Gu Hwan} and Osborn, {Mark J.} and Jakub Tolar and Yoo, {Han Wook} and Lee, {Beom Hee}",
year = "2020",
month = "1",
day = "1",
doi = "10.1038/s10038-019-0695-0",
language = "English (US)",
volume = "65",
pages = "79--89",
journal = "Journal of Human Genetics",
issn = "1434-5161",
publisher = "Nature Publishing Group",
number = "2",

}

TY - JOUR

T1 - Phenotype categorization of neurofibromatosis type I and correlation to NF1 mutation types

AU - Kang, Eungu

AU - Kim, Yoon Myung

AU - Seo, Go Hun

AU - Oh, Arum

AU - Yoon, Hee Mang

AU - Ra, Young Shin

AU - Kim, Eun Key

AU - Kim, Heyry

AU - Heo, Sun Hee

AU - Kim, Gu Hwan

AU - Osborn, Mark J.

AU - Tolar, Jakub

AU - Yoo, Han Wook

AU - Lee, Beom Hee

PY - 2020/1/1

Y1 - 2020/1/1

N2 - 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.

AB - 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.

UR - http://www.scopus.com/inward/record.url?scp=85075941112&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=85075941112&partnerID=8YFLogxK

U2 - 10.1038/s10038-019-0695-0

DO - 10.1038/s10038-019-0695-0

M3 - Article

C2 - 31776437

AN - SCOPUS:85075941112

VL - 65

SP - 79

EP - 89

JO - Journal of Human Genetics

JF - Journal of Human Genetics

SN - 1434-5161

IS - 2

ER -