Naegeli-Franceschetti-Jadassohn syndrome and dermatopathia pigmentosa reticularis: Two allelic ectodermal dysplasias caused by dominant mutations in KRT14

Jennie Lugassy, Peter Itin, Akemi Ishida-Yamamoto, Kristen Holland, Susan Huson, Dan Geiger, Hans Christian Hennies, Margarita Indelman, Dani Bercovich, Jouni Uitto, Reuven Bergman, John A. McGrath, Gabriele Richard, Eli Sprecher

Research output: Contribution to journalArticle

80 Citations (Scopus)

Abstract

Naegeli-Franceschetti-Jadassohn syndrome (NFJS) and dermatopathia pigmentosa reticularis (DPR) are two closely related autosomal dominant ectodermal dysplasia syndromes that clinically share complete absence of dermatoglyphics (fingerprint lines), a reticulate pattern of skin hyperpigmentation, thickening of the palms and soles (palmoplantar keratoderma), abnormal sweating, and other subtle developmental anomalies of the teeth, hair, and skin. To decipher the molecular basis of these disorders, we studied one family with DPR and four families with NFJS. We initially reassessed linkage of NFJS/DPR to a previously established locus on 17q11.2-q21. Combined multipoint analysis generated a maximal LOD score of 8.3 at marker D17S800 at a recombination fraction of 0. The disease interval was found to harbor 230 genes, including a large cluster of keratin genes. Heterozygous nonsense or frameshift mutations in KRT14 were found to segregate with the disease trait in all five families. In contrast with KRT14 mutations affecting the central α-helical rod domain of keratin 14, which are known to cause epidermolysis bullosa simplex, NFJS/DPR-associated mutations were found in a region of the gene encoding the nonhelical head (E1/V1) domain and are predicted to result in very early termination of translation. These data suggest that KRT14 plays an important role during ontogenesis of dermatoglyphics and sweat glands. Among other functions, the N-terminal part of keratin molecules has been shown to confer protection against proapoptotic signals. Ultrastructural examination of patient skin biopsy specimens provided evidence for increased apoptotic activity in the basal cell layer where KRT14 is expressed, suggesting that apoptosis is an important mechanism in the pathogenesis of NFJS/DPR.

LanguageEnglish
Pages724-730
Number of pages7
JournalAmerican Journal of Human Genetics
Volume79
Issue number4
DOIs
Publication statusPublished - 1 Jan 2006
Externally publishedYes

Fingerprint

Ectodermal Dysplasia
Mutation
Dermatoglyphics
Keratins
Skin
Epidermolysis Bullosa Simplex
Palmoplantar Keratoderma
Keratin-14
Sweat Glands
Hyperpigmentation
Frameshift Mutation
Sweating
Nonsense Codon
Multigene Family
Hair
Genetic Recombination
Genes
Tooth
Head
Dermatopathia pigmentosa reticularis

Cite this

Lugassy, Jennie ; Itin, Peter ; Ishida-Yamamoto, Akemi ; Holland, Kristen ; Huson, Susan ; Geiger, Dan ; Hennies, Hans Christian ; Indelman, Margarita ; Bercovich, Dani ; Uitto, Jouni ; Bergman, Reuven ; McGrath, John A. ; Richard, Gabriele ; Sprecher, Eli. / Naegeli-Franceschetti-Jadassohn syndrome and dermatopathia pigmentosa reticularis : Two allelic ectodermal dysplasias caused by dominant mutations in KRT14. In: American Journal of Human Genetics. 2006 ; Vol. 79, No. 4. pp. 724-730.
@article{541077de1ca148d3971ed329f3feea84,
title = "Naegeli-Franceschetti-Jadassohn syndrome and dermatopathia pigmentosa reticularis: Two allelic ectodermal dysplasias caused by dominant mutations in KRT14",
abstract = "Naegeli-Franceschetti-Jadassohn syndrome (NFJS) and dermatopathia pigmentosa reticularis (DPR) are two closely related autosomal dominant ectodermal dysplasia syndromes that clinically share complete absence of dermatoglyphics (fingerprint lines), a reticulate pattern of skin hyperpigmentation, thickening of the palms and soles (palmoplantar keratoderma), abnormal sweating, and other subtle developmental anomalies of the teeth, hair, and skin. To decipher the molecular basis of these disorders, we studied one family with DPR and four families with NFJS. We initially reassessed linkage of NFJS/DPR to a previously established locus on 17q11.2-q21. Combined multipoint analysis generated a maximal LOD score of 8.3 at marker D17S800 at a recombination fraction of 0. The disease interval was found to harbor 230 genes, including a large cluster of keratin genes. Heterozygous nonsense or frameshift mutations in KRT14 were found to segregate with the disease trait in all five families. In contrast with KRT14 mutations affecting the central α-helical rod domain of keratin 14, which are known to cause epidermolysis bullosa simplex, NFJS/DPR-associated mutations were found in a region of the gene encoding the nonhelical head (E1/V1) domain and are predicted to result in very early termination of translation. These data suggest that KRT14 plays an important role during ontogenesis of dermatoglyphics and sweat glands. Among other functions, the N-terminal part of keratin molecules has been shown to confer protection against proapoptotic signals. Ultrastructural examination of patient skin biopsy specimens provided evidence for increased apoptotic activity in the basal cell layer where KRT14 is expressed, suggesting that apoptosis is an important mechanism in the pathogenesis of NFJS/DPR.",
author = "Jennie Lugassy and Peter Itin and Akemi Ishida-Yamamoto and Kristen Holland and Susan Huson and Dan Geiger and Hennies, {Hans Christian} and Margarita Indelman and Dani Bercovich and Jouni Uitto and Reuven Bergman and McGrath, {John A.} and Gabriele Richard and Eli Sprecher",
year = "2006",
month = "1",
day = "1",
doi = "10.1086/507792",
language = "English",
volume = "79",
pages = "724--730",
journal = "American Journal of Human Genetics",
issn = "0002-9297",
publisher = "Cell Press",
number = "4",

}

Lugassy, J, Itin, P, Ishida-Yamamoto, A, Holland, K, Huson, S, Geiger, D, Hennies, HC, Indelman, M, Bercovich, D, Uitto, J, Bergman, R, McGrath, JA, Richard, G & Sprecher, E 2006, 'Naegeli-Franceschetti-Jadassohn syndrome and dermatopathia pigmentosa reticularis: Two allelic ectodermal dysplasias caused by dominant mutations in KRT14', American Journal of Human Genetics, vol. 79, no. 4, pp. 724-730. https://doi.org/10.1086/507792

Naegeli-Franceschetti-Jadassohn syndrome and dermatopathia pigmentosa reticularis : Two allelic ectodermal dysplasias caused by dominant mutations in KRT14. / Lugassy, Jennie; Itin, Peter; Ishida-Yamamoto, Akemi; Holland, Kristen; Huson, Susan; Geiger, Dan; Hennies, Hans Christian; Indelman, Margarita; Bercovich, Dani; Uitto, Jouni; Bergman, Reuven; McGrath, John A.; Richard, Gabriele; Sprecher, Eli.

In: American Journal of Human Genetics, Vol. 79, No. 4, 01.01.2006, p. 724-730.

Research output: Contribution to journalArticle

TY - JOUR

T1 - Naegeli-Franceschetti-Jadassohn syndrome and dermatopathia pigmentosa reticularis

T2 - American Journal of Human Genetics

AU - Lugassy, Jennie

AU - Itin, Peter

AU - Ishida-Yamamoto, Akemi

AU - Holland, Kristen

AU - Huson, Susan

AU - Geiger, Dan

AU - Hennies, Hans Christian

AU - Indelman, Margarita

AU - Bercovich, Dani

AU - Uitto, Jouni

AU - Bergman, Reuven

AU - McGrath, John A.

AU - Richard, Gabriele

AU - Sprecher, Eli

PY - 2006/1/1

Y1 - 2006/1/1

N2 - Naegeli-Franceschetti-Jadassohn syndrome (NFJS) and dermatopathia pigmentosa reticularis (DPR) are two closely related autosomal dominant ectodermal dysplasia syndromes that clinically share complete absence of dermatoglyphics (fingerprint lines), a reticulate pattern of skin hyperpigmentation, thickening of the palms and soles (palmoplantar keratoderma), abnormal sweating, and other subtle developmental anomalies of the teeth, hair, and skin. To decipher the molecular basis of these disorders, we studied one family with DPR and four families with NFJS. We initially reassessed linkage of NFJS/DPR to a previously established locus on 17q11.2-q21. Combined multipoint analysis generated a maximal LOD score of 8.3 at marker D17S800 at a recombination fraction of 0. The disease interval was found to harbor 230 genes, including a large cluster of keratin genes. Heterozygous nonsense or frameshift mutations in KRT14 were found to segregate with the disease trait in all five families. In contrast with KRT14 mutations affecting the central α-helical rod domain of keratin 14, which are known to cause epidermolysis bullosa simplex, NFJS/DPR-associated mutations were found in a region of the gene encoding the nonhelical head (E1/V1) domain and are predicted to result in very early termination of translation. These data suggest that KRT14 plays an important role during ontogenesis of dermatoglyphics and sweat glands. Among other functions, the N-terminal part of keratin molecules has been shown to confer protection against proapoptotic signals. Ultrastructural examination of patient skin biopsy specimens provided evidence for increased apoptotic activity in the basal cell layer where KRT14 is expressed, suggesting that apoptosis is an important mechanism in the pathogenesis of NFJS/DPR.

AB - Naegeli-Franceschetti-Jadassohn syndrome (NFJS) and dermatopathia pigmentosa reticularis (DPR) are two closely related autosomal dominant ectodermal dysplasia syndromes that clinically share complete absence of dermatoglyphics (fingerprint lines), a reticulate pattern of skin hyperpigmentation, thickening of the palms and soles (palmoplantar keratoderma), abnormal sweating, and other subtle developmental anomalies of the teeth, hair, and skin. To decipher the molecular basis of these disorders, we studied one family with DPR and four families with NFJS. We initially reassessed linkage of NFJS/DPR to a previously established locus on 17q11.2-q21. Combined multipoint analysis generated a maximal LOD score of 8.3 at marker D17S800 at a recombination fraction of 0. The disease interval was found to harbor 230 genes, including a large cluster of keratin genes. Heterozygous nonsense or frameshift mutations in KRT14 were found to segregate with the disease trait in all five families. In contrast with KRT14 mutations affecting the central α-helical rod domain of keratin 14, which are known to cause epidermolysis bullosa simplex, NFJS/DPR-associated mutations were found in a region of the gene encoding the nonhelical head (E1/V1) domain and are predicted to result in very early termination of translation. These data suggest that KRT14 plays an important role during ontogenesis of dermatoglyphics and sweat glands. Among other functions, the N-terminal part of keratin molecules has been shown to confer protection against proapoptotic signals. Ultrastructural examination of patient skin biopsy specimens provided evidence for increased apoptotic activity in the basal cell layer where KRT14 is expressed, suggesting that apoptosis is an important mechanism in the pathogenesis of NFJS/DPR.

UR - http://www.scopus.com/inward/record.url?scp=33749035448&partnerID=8YFLogxK

U2 - 10.1086/507792

DO - 10.1086/507792

M3 - Article

VL - 79

SP - 724

EP - 730

JO - American Journal of Human Genetics

JF - American Journal of Human Genetics

SN - 0002-9297

IS - 4

ER -