Novel and recurrent mutations in the genes encoding keratins k6a, k16 and k17 in 13 cases of pachyonychia congenita

A. Terrinoni, F. J D Smith, B. Didona, F. Canzona, M. Paradisi, M. Huber, D. Hohl, A. David, A. Verloes, I. M. Leigh, C. S. Munro, G. Melino, W. H I McLean

Research output: Contribution to journalArticle

51 Citations (Scopus)

Abstract

Thirteen patients with pachyonychia congenita types 1 and 2 were studied, two of which had a family history of pachyonychia and 11 of which were sporadic cases. Heterozygous mis-sense or small in-frame insertion/deletion mutations were detected in the genes encoding keratins K6a, K16, and K17 in all cases. Three novel mutations, F174V, E472K, and L469R were found in the K6a gene. Two novel mutations, M121T and L128Q were detected in K16. Similarly, three novel mutations, L95P, S97del, and L99P were found in K17. In addition, we identified recurrent mutations N171del (three instances) and F174S in K6a and R94H in K17. Analysis of both phenotype and genotype data led to the following conclusions: (i) K6a or K16 mutations produce the pachyonychia congenita type 1 phenotype, whereas K17 (or K6b) mutations cause pachyonychia congenita type 2; (ii) the presence of pilosebaceous cysts following puberty is the best indicator of pachyonychia congenita type 2; (iii) prepubescent patients are more difficult to classify due to the lack of cysts; and (iv) natal teeth are indicative of pachyonychia congenita type 2, although their absence does not preclude the pachyonychia congenita type 2 phenotype. This study establishes useful diagnostic criteria for pachyonychia congenita types 1 and 2, which will help limit unnecessary DNA analysis in the diagnosis and management of this genetically heterogeneous group of genodermatoses.

Original languageEnglish
Pages (from-to)1391-1396
Number of pages6
JournalJournal of Investigative Dermatology
Volume117
Issue number6
DOIs
Publication statusPublished - 2001

Fingerprint

Pachyonychia Congenita
Gene encoding
Keratins
Genes
Mutation
DNA
Phenotype
Cysts
Natal Teeth
Malformed Nails
INDEL Mutation
Puberty
Genotype

Keywords

  • Genodermatoses
  • Keratin
  • Mutation
  • Nail dystrophy
  • Pachyonychia congenita

ASJC Scopus subject areas

  • Dermatology

Cite this

Terrinoni, A., Smith, F. J. D., Didona, B., Canzona, F., Paradisi, M., Huber, M., ... McLean, W. H. I. (2001). Novel and recurrent mutations in the genes encoding keratins k6a, k16 and k17 in 13 cases of pachyonychia congenita. Journal of Investigative Dermatology, 117(6), 1391-1396. https://doi.org/10.1046/j.0022-202x.2001.01565.x

Novel and recurrent mutations in the genes encoding keratins k6a, k16 and k17 in 13 cases of pachyonychia congenita. / Terrinoni, A.; Smith, F. J D; Didona, B.; Canzona, F.; Paradisi, M.; Huber, M.; Hohl, D.; David, A.; Verloes, A.; Leigh, I. M.; Munro, C. S.; Melino, G.; McLean, W. H I.

In: Journal of Investigative Dermatology, Vol. 117, No. 6, 2001, p. 1391-1396.

Research output: Contribution to journalArticle

Terrinoni, A, Smith, FJD, Didona, B, Canzona, F, Paradisi, M, Huber, M, Hohl, D, David, A, Verloes, A, Leigh, IM, Munro, CS, Melino, G & McLean, WHI 2001, 'Novel and recurrent mutations in the genes encoding keratins k6a, k16 and k17 in 13 cases of pachyonychia congenita', Journal of Investigative Dermatology, vol. 117, no. 6, pp. 1391-1396. https://doi.org/10.1046/j.0022-202x.2001.01565.x
Terrinoni, A. ; Smith, F. J D ; Didona, B. ; Canzona, F. ; Paradisi, M. ; Huber, M. ; Hohl, D. ; David, A. ; Verloes, A. ; Leigh, I. M. ; Munro, C. S. ; Melino, G. ; McLean, W. H I. / Novel and recurrent mutations in the genes encoding keratins k6a, k16 and k17 in 13 cases of pachyonychia congenita. In: Journal of Investigative Dermatology. 2001 ; Vol. 117, No. 6. pp. 1391-1396.
@article{d7705e6d50e84b97b15aa7605b33f62a,
title = "Novel and recurrent mutations in the genes encoding keratins k6a, k16 and k17 in 13 cases of pachyonychia congenita",
abstract = "Thirteen patients with pachyonychia congenita types 1 and 2 were studied, two of which had a family history of pachyonychia and 11 of which were sporadic cases. Heterozygous mis-sense or small in-frame insertion/deletion mutations were detected in the genes encoding keratins K6a, K16, and K17 in all cases. Three novel mutations, F174V, E472K, and L469R were found in the K6a gene. Two novel mutations, M121T and L128Q were detected in K16. Similarly, three novel mutations, L95P, S97del, and L99P were found in K17. In addition, we identified recurrent mutations N171del (three instances) and F174S in K6a and R94H in K17. Analysis of both phenotype and genotype data led to the following conclusions: (i) K6a or K16 mutations produce the pachyonychia congenita type 1 phenotype, whereas K17 (or K6b) mutations cause pachyonychia congenita type 2; (ii) the presence of pilosebaceous cysts following puberty is the best indicator of pachyonychia congenita type 2; (iii) prepubescent patients are more difficult to classify due to the lack of cysts; and (iv) natal teeth are indicative of pachyonychia congenita type 2, although their absence does not preclude the pachyonychia congenita type 2 phenotype. This study establishes useful diagnostic criteria for pachyonychia congenita types 1 and 2, which will help limit unnecessary DNA analysis in the diagnosis and management of this genetically heterogeneous group of genodermatoses.",
keywords = "Genodermatoses, Keratin, Mutation, Nail dystrophy, Pachyonychia congenita",
author = "A. Terrinoni and Smith, {F. J D} and B. Didona and F. Canzona and M. Paradisi and M. Huber and D. Hohl and A. David and A. Verloes and Leigh, {I. M.} and Munro, {C. S.} and G. Melino and McLean, {W. H I}",
year = "2001",
doi = "10.1046/j.0022-202x.2001.01565.x",
language = "English",
volume = "117",
pages = "1391--1396",
journal = "Journal of Investigative Dermatology",
issn = "0022-202X",
publisher = "Nature Publishing Group",
number = "6",

}

TY - JOUR

T1 - Novel and recurrent mutations in the genes encoding keratins k6a, k16 and k17 in 13 cases of pachyonychia congenita

AU - Terrinoni, A.

AU - Smith, F. J D

AU - Didona, B.

AU - Canzona, F.

AU - Paradisi, M.

AU - Huber, M.

AU - Hohl, D.

AU - David, A.

AU - Verloes, A.

AU - Leigh, I. M.

AU - Munro, C. S.

AU - Melino, G.

AU - McLean, W. H I

PY - 2001

Y1 - 2001

N2 - Thirteen patients with pachyonychia congenita types 1 and 2 were studied, two of which had a family history of pachyonychia and 11 of which were sporadic cases. Heterozygous mis-sense or small in-frame insertion/deletion mutations were detected in the genes encoding keratins K6a, K16, and K17 in all cases. Three novel mutations, F174V, E472K, and L469R were found in the K6a gene. Two novel mutations, M121T and L128Q were detected in K16. Similarly, three novel mutations, L95P, S97del, and L99P were found in K17. In addition, we identified recurrent mutations N171del (three instances) and F174S in K6a and R94H in K17. Analysis of both phenotype and genotype data led to the following conclusions: (i) K6a or K16 mutations produce the pachyonychia congenita type 1 phenotype, whereas K17 (or K6b) mutations cause pachyonychia congenita type 2; (ii) the presence of pilosebaceous cysts following puberty is the best indicator of pachyonychia congenita type 2; (iii) prepubescent patients are more difficult to classify due to the lack of cysts; and (iv) natal teeth are indicative of pachyonychia congenita type 2, although their absence does not preclude the pachyonychia congenita type 2 phenotype. This study establishes useful diagnostic criteria for pachyonychia congenita types 1 and 2, which will help limit unnecessary DNA analysis in the diagnosis and management of this genetically heterogeneous group of genodermatoses.

AB - Thirteen patients with pachyonychia congenita types 1 and 2 were studied, two of which had a family history of pachyonychia and 11 of which were sporadic cases. Heterozygous mis-sense or small in-frame insertion/deletion mutations were detected in the genes encoding keratins K6a, K16, and K17 in all cases. Three novel mutations, F174V, E472K, and L469R were found in the K6a gene. Two novel mutations, M121T and L128Q were detected in K16. Similarly, three novel mutations, L95P, S97del, and L99P were found in K17. In addition, we identified recurrent mutations N171del (three instances) and F174S in K6a and R94H in K17. Analysis of both phenotype and genotype data led to the following conclusions: (i) K6a or K16 mutations produce the pachyonychia congenita type 1 phenotype, whereas K17 (or K6b) mutations cause pachyonychia congenita type 2; (ii) the presence of pilosebaceous cysts following puberty is the best indicator of pachyonychia congenita type 2; (iii) prepubescent patients are more difficult to classify due to the lack of cysts; and (iv) natal teeth are indicative of pachyonychia congenita type 2, although their absence does not preclude the pachyonychia congenita type 2 phenotype. This study establishes useful diagnostic criteria for pachyonychia congenita types 1 and 2, which will help limit unnecessary DNA analysis in the diagnosis and management of this genetically heterogeneous group of genodermatoses.

KW - Genodermatoses

KW - Keratin

KW - Mutation

KW - Nail dystrophy

KW - Pachyonychia congenita

UR - http://www.scopus.com/inward/record.url?scp=0035670863&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=0035670863&partnerID=8YFLogxK

U2 - 10.1046/j.0022-202x.2001.01565.x

DO - 10.1046/j.0022-202x.2001.01565.x

M3 - Article

C2 - 11886499

AN - SCOPUS:0035670863

VL - 117

SP - 1391

EP - 1396

JO - Journal of Investigative Dermatology

JF - Journal of Investigative Dermatology

SN - 0022-202X

IS - 6

ER -