Two novel recessive mutations in KRT14 identified in a cohort of 21 Spanish families with epidermolysis bullosa simplex

M. García, J. L. Santiago, A. Terrõn, A. Hernández-Martín, A. Vicente, C. Fortuny, R. De Lucas, J. C. Lõpez, N. Cuadrado-Corrales, A. Holguín, N. Illera, B. Duarte, C. Sánchez-Jimeno, S. Llames, E. García, C. Ayuso, L. Martínez-Santamaría, D. Castiglia, N. De Luca, A. TorreloD. Mechan, D. Baty, G. Zambruno, M. J. Escámez, M. Del Río

Research output: Contribution to journalArticle

Abstract

Summary Background Basal epidermolysis bullosa simplex (EBS) is a group of blistering genodermatoses mostly caused by mutations in the keratin genes, KRT5 and KRT14. Recessive mutations represent about 5% of all EBS mutations, being common and specific in populations with high consanguinity, where affected patients show severe phenotypes. Objectives To accomplish the first mutational analysis in patients of Spanish origin with EBS and to delineate a comprehensive genotype-phenotype correlation. Methods Twenty-one EBS families were analysed. Immunofluorescence mapping at the dermoepidermal junction level was performed on skin biopsies from patients. Mutation screening of the entire coding sequences of KRT5 and KRT14 in genomic DNA was assessed by polymerase chain reaction and direct sequencing. Results KRT5 or KRT14 causative mutations were identified in 18 of the 21 EBS families. A total of 14 different mutations were disclosed, of which 12 were dominant missense mutations and two truncating recessive mutations. Five of the 14 mutations were novel including three dominant in KRT5 (p.V186E, p.T321P and p.A428T) and two recessive in KRT14 (p.K116X and p.K250RfsX8). The two patients with EBS carrying homozygous recessive mutations were affected by severe phenotypes and belonged to consanguineous families. All five families with the EBS Dowling-Meara subtype carried recurrent mutations affecting the highly conserved ends of the α-helical rod domain of K5 and K14. The seven mutations associated with the localized EBS subtype were widely distributed along the KRT5 and KRT14 genes. Two families with mottled pigmentation carried the P25L mutation in KRT5, commonly associated with this subtype. Conclusions This study further confirms the genotype-phenotype correlation established for EBS in other ethnic groups, and is the first in a Mediterranean country (excluding Israel). This study adds two novel recessive mutations to the worldwide record to date, which includes a total of 14 mutations. As in previous reports, the recessive mutations resulted in a lack of keratin K14, giving rise to a generalized and severe presentation.

Original languageEnglish
Pages (from-to)683-692
Number of pages10
JournalBritish Journal of Dermatology
Volume165
Issue number3
DOIs
Publication statusPublished - Sep 2011

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Epidermolysis Bullosa Simplex
Mutation
Genetic Association Studies
Keratins
Phenotype
Consanguinity

ASJC Scopus subject areas

  • Dermatology

Cite this

García, M., Santiago, J. L., Terrõn, A., Hernández-Martín, A., Vicente, A., Fortuny, C., ... Del Río, M. (2011). Two novel recessive mutations in KRT14 identified in a cohort of 21 Spanish families with epidermolysis bullosa simplex. British Journal of Dermatology, 165(3), 683-692. https://doi.org/10.1111/j.1365-2133.2011.10428.x

Two novel recessive mutations in KRT14 identified in a cohort of 21 Spanish families with epidermolysis bullosa simplex. / García, M.; Santiago, J. L.; Terrõn, A.; Hernández-Martín, A.; Vicente, A.; Fortuny, C.; De Lucas, R.; Lõpez, J. C.; Cuadrado-Corrales, N.; Holguín, A.; Illera, N.; Duarte, B.; Sánchez-Jimeno, C.; Llames, S.; García, E.; Ayuso, C.; Martínez-Santamaría, L.; Castiglia, D.; De Luca, N.; Torrelo, A.; Mechan, D.; Baty, D.; Zambruno, G.; Escámez, M. J.; Del Río, M.

In: British Journal of Dermatology, Vol. 165, No. 3, 09.2011, p. 683-692.

Research output: Contribution to journalArticle

García, M, Santiago, JL, Terrõn, A, Hernández-Martín, A, Vicente, A, Fortuny, C, De Lucas, R, Lõpez, JC, Cuadrado-Corrales, N, Holguín, A, Illera, N, Duarte, B, Sánchez-Jimeno, C, Llames, S, García, E, Ayuso, C, Martínez-Santamaría, L, Castiglia, D, De Luca, N, Torrelo, A, Mechan, D, Baty, D, Zambruno, G, Escámez, MJ & Del Río, M 2011, 'Two novel recessive mutations in KRT14 identified in a cohort of 21 Spanish families with epidermolysis bullosa simplex', British Journal of Dermatology, vol. 165, no. 3, pp. 683-692. https://doi.org/10.1111/j.1365-2133.2011.10428.x
García, M. ; Santiago, J. L. ; Terrõn, A. ; Hernández-Martín, A. ; Vicente, A. ; Fortuny, C. ; De Lucas, R. ; Lõpez, J. C. ; Cuadrado-Corrales, N. ; Holguín, A. ; Illera, N. ; Duarte, B. ; Sánchez-Jimeno, C. ; Llames, S. ; García, E. ; Ayuso, C. ; Martínez-Santamaría, L. ; Castiglia, D. ; De Luca, N. ; Torrelo, A. ; Mechan, D. ; Baty, D. ; Zambruno, G. ; Escámez, M. J. ; Del Río, M. / Two novel recessive mutations in KRT14 identified in a cohort of 21 Spanish families with epidermolysis bullosa simplex. In: British Journal of Dermatology. 2011 ; Vol. 165, No. 3. pp. 683-692.
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abstract = "Summary Background Basal epidermolysis bullosa simplex (EBS) is a group of blistering genodermatoses mostly caused by mutations in the keratin genes, KRT5 and KRT14. Recessive mutations represent about 5{\%} of all EBS mutations, being common and specific in populations with high consanguinity, where affected patients show severe phenotypes. Objectives To accomplish the first mutational analysis in patients of Spanish origin with EBS and to delineate a comprehensive genotype-phenotype correlation. Methods Twenty-one EBS families were analysed. Immunofluorescence mapping at the dermoepidermal junction level was performed on skin biopsies from patients. Mutation screening of the entire coding sequences of KRT5 and KRT14 in genomic DNA was assessed by polymerase chain reaction and direct sequencing. Results KRT5 or KRT14 causative mutations were identified in 18 of the 21 EBS families. A total of 14 different mutations were disclosed, of which 12 were dominant missense mutations and two truncating recessive mutations. Five of the 14 mutations were novel including three dominant in KRT5 (p.V186E, p.T321P and p.A428T) and two recessive in KRT14 (p.K116X and p.K250RfsX8). The two patients with EBS carrying homozygous recessive mutations were affected by severe phenotypes and belonged to consanguineous families. All five families with the EBS Dowling-Meara subtype carried recurrent mutations affecting the highly conserved ends of the α-helical rod domain of K5 and K14. The seven mutations associated with the localized EBS subtype were widely distributed along the KRT5 and KRT14 genes. Two families with mottled pigmentation carried the P25L mutation in KRT5, commonly associated with this subtype. Conclusions This study further confirms the genotype-phenotype correlation established for EBS in other ethnic groups, and is the first in a Mediterranean country (excluding Israel). This study adds two novel recessive mutations to the worldwide record to date, which includes a total of 14 mutations. As in previous reports, the recessive mutations resulted in a lack of keratin K14, giving rise to a generalized and severe presentation.",
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T1 - Two novel recessive mutations in KRT14 identified in a cohort of 21 Spanish families with epidermolysis bullosa simplex

AU - García, M.

AU - Santiago, J. L.

AU - Terrõn, A.

AU - Hernández-Martín, A.

AU - Vicente, A.

AU - Fortuny, C.

AU - De Lucas, R.

AU - Lõpez, J. C.

AU - Cuadrado-Corrales, N.

AU - Holguín, A.

AU - Illera, N.

AU - Duarte, B.

AU - Sánchez-Jimeno, C.

AU - Llames, S.

AU - García, E.

AU - Ayuso, C.

AU - Martínez-Santamaría, L.

AU - Castiglia, D.

AU - De Luca, N.

AU - Torrelo, A.

AU - Mechan, D.

AU - Baty, D.

AU - Zambruno, G.

AU - Escámez, M. J.

AU - Del Río, M.

PY - 2011/9

Y1 - 2011/9

N2 - Summary Background Basal epidermolysis bullosa simplex (EBS) is a group of blistering genodermatoses mostly caused by mutations in the keratin genes, KRT5 and KRT14. Recessive mutations represent about 5% of all EBS mutations, being common and specific in populations with high consanguinity, where affected patients show severe phenotypes. Objectives To accomplish the first mutational analysis in patients of Spanish origin with EBS and to delineate a comprehensive genotype-phenotype correlation. Methods Twenty-one EBS families were analysed. Immunofluorescence mapping at the dermoepidermal junction level was performed on skin biopsies from patients. Mutation screening of the entire coding sequences of KRT5 and KRT14 in genomic DNA was assessed by polymerase chain reaction and direct sequencing. Results KRT5 or KRT14 causative mutations were identified in 18 of the 21 EBS families. A total of 14 different mutations were disclosed, of which 12 were dominant missense mutations and two truncating recessive mutations. Five of the 14 mutations were novel including three dominant in KRT5 (p.V186E, p.T321P and p.A428T) and two recessive in KRT14 (p.K116X and p.K250RfsX8). The two patients with EBS carrying homozygous recessive mutations were affected by severe phenotypes and belonged to consanguineous families. All five families with the EBS Dowling-Meara subtype carried recurrent mutations affecting the highly conserved ends of the α-helical rod domain of K5 and K14. The seven mutations associated with the localized EBS subtype were widely distributed along the KRT5 and KRT14 genes. Two families with mottled pigmentation carried the P25L mutation in KRT5, commonly associated with this subtype. Conclusions This study further confirms the genotype-phenotype correlation established for EBS in other ethnic groups, and is the first in a Mediterranean country (excluding Israel). This study adds two novel recessive mutations to the worldwide record to date, which includes a total of 14 mutations. As in previous reports, the recessive mutations resulted in a lack of keratin K14, giving rise to a generalized and severe presentation.

AB - Summary Background Basal epidermolysis bullosa simplex (EBS) is a group of blistering genodermatoses mostly caused by mutations in the keratin genes, KRT5 and KRT14. Recessive mutations represent about 5% of all EBS mutations, being common and specific in populations with high consanguinity, where affected patients show severe phenotypes. Objectives To accomplish the first mutational analysis in patients of Spanish origin with EBS and to delineate a comprehensive genotype-phenotype correlation. Methods Twenty-one EBS families were analysed. Immunofluorescence mapping at the dermoepidermal junction level was performed on skin biopsies from patients. Mutation screening of the entire coding sequences of KRT5 and KRT14 in genomic DNA was assessed by polymerase chain reaction and direct sequencing. Results KRT5 or KRT14 causative mutations were identified in 18 of the 21 EBS families. A total of 14 different mutations were disclosed, of which 12 were dominant missense mutations and two truncating recessive mutations. Five of the 14 mutations were novel including three dominant in KRT5 (p.V186E, p.T321P and p.A428T) and two recessive in KRT14 (p.K116X and p.K250RfsX8). The two patients with EBS carrying homozygous recessive mutations were affected by severe phenotypes and belonged to consanguineous families. All five families with the EBS Dowling-Meara subtype carried recurrent mutations affecting the highly conserved ends of the α-helical rod domain of K5 and K14. The seven mutations associated with the localized EBS subtype were widely distributed along the KRT5 and KRT14 genes. Two families with mottled pigmentation carried the P25L mutation in KRT5, commonly associated with this subtype. Conclusions This study further confirms the genotype-phenotype correlation established for EBS in other ethnic groups, and is the first in a Mediterranean country (excluding Israel). This study adds two novel recessive mutations to the worldwide record to date, which includes a total of 14 mutations. As in previous reports, the recessive mutations resulted in a lack of keratin K14, giving rise to a generalized and severe presentation.

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