Autosomal recessive pure hair and nail ectodermal dysplasia linked to chromosome 12p11.1-q14.3 without KRTHB5 gene mutation

Rasool, Mahmood; Nawaz, Sadia; Azhar, Aisha; Wajid, Muhammad; Westermark, Per; Baig, Shahid Mahmood; Klar, Joakim; Dahl, Niklas

doi:10.1684/ejd.2010.0962

Cited by 10 publications

(14 citation statements)

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“…The pedigree was slightly modified from the previous report [2] (Figure 1A). Written informed consent was obtained from all participating individuals or their legal guardians and the study was approved by the local ethical committee at the National Institute for Biotechnology and Genetic Engineering (NIBGE), Faisalabad, Pakistan.…”

Section: Methodsmentioning

confidence: 99%

“…(A) Pedigree of the consanguineous Pakistani family with PHNED (modified from [2]). Affected individuals are represented by filled symbols.…”

Section: Methodsmentioning

confidence: 99%

“…Ectodermal dysplasias (EDs) comprise a heterogeneous group of developmental disorders involving two or more ectodermal appendages [1], [2]. Pure hair and nail ectodermal dysplasia (PHNED (MIM 602032, 614929 and 614931)) is a rare subgroup of EDs characterized by nail dystrophy, brittle hair and hypotrichosis.…”

Section: Introductionmentioning

confidence: 99%

“…In the present study, we re-investigated a consanguineous Pakistani family segregating AR PHNED previously linked to chromosome 12p11.1-q14.3 (MIM 614929) [2]. The region coincides with the type II keratin gene cluster and spans both the KRT85 and the HOXC13 genes.…”

Section: Introductionmentioning

confidence: 99%

“…The region coincides with the type II keratin gene cluster and spans both the KRT85 and the HOXC13 genes. Analysis of the entire coding region of KRT85 did not reveal any mutation [2] and we therefore analyzed HOXC13 and the rest of the approximately 480 linked genes by exome sequencing. The combined results from our study indicate that the KRT74 gene is a second member of the keratin II gene cluster associated with AR PHNED.…”

Section: Introductionmentioning

confidence: 99%

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Autosomal Recessive Transmission of a Rare KRT74 Variant Causes Hair and Nail Ectodermal Dysplasia: Allelism with Dominant Woolly Hair/Hypotrichosis

et al. 2014

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Pure hair and nail ectodermal dysplasia (PHNED) comprises a heterogeneous group of rare heritable disorders characterized by brittle hair, hypotrichosis, onychodystrophy and micronychia. Autosomal recessive (AR) PHNED has previously been associated with mutations in either KRT85 or HOXC13 on chromosome 12p11.1-q14.3. We investigated a consanguineous Pakistani family with AR PHNED linked to the keratin gene cluster on 12p11.1 but without detectable mutations in KRT85 and HOXC13. Whole exome sequencing of affected individuals revealed homozygosity for a rare c.821T>C variant (p.Phe274Ser) in the KRT74 gene that segregates AR PHNED in the family. The transition alters the highly conserved Phe274 residue in the coil 1B domain required for long-range dimerization of keratins, suggesting that the mutation compromises the stability of intermediate filaments. Immunohistochemical (IHC) analyses confirmed a strong keratin-74 expression in the nail matrix, the nail bed and the hyponychium of mouse distal digits, as well as in normal human hair follicles. Furthermore, hair follicles and epidermis of an affected family member stained negative for Keratin-74 suggesting a loss of function mechanism mediated by the Phe274Ser substitution. Our observations show for the first time that homozygosity for a KRT74 missense variant may be associated with AR PHNED. Heterozygous KRT74 mutations have previously been associated with autosomal dominant woolly hair/hypotrichosis simplex (ADWH). Thus, our findings expand the phenotypic spectrum associated with KRT74 mutations and imply that a subtype of AR PHNED is allelic with ADWH.

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Section: Methodsmentioning

confidence: 99%

“…(A) Pedigree of the consanguineous Pakistani family with PHNED (modified from [2]). Affected individuals are represented by filled symbols.…”

Section: Methodsmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

See 3 more Smart Citations

Autosomal Recessive Transmission of a Rare KRT74 Variant Causes Hair and Nail Ectodermal Dysplasia: Allelism with Dominant Woolly Hair/Hypotrichosis

et al. 2014

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Review of Keratin Disorders

Steensel

Steijlen

2019

Harper's Textbook of Pediatric Dermatology

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A Homozygous Frameshift Mutation in theHOXC13Gene Underlies Pure Hair and Nail Ectodermal Dysplasia in a Syrian Family

Farooq

Kurban²,

Fujimoto³

et al. 2013

Human Mutation

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Pure hair and nail ectodermal dysplasia (PHNED) is a rare genetic disorder characterized by hypotrichosis or complete alopecia, as well as nail dystrophy. Mutations in the type II hair keratin gene KRT85 and the HOXC13 gene on chromosome 12q have recently been identified in families with autosomal-recessive PHNED. In the present study, we have analyzed a consanguineous Syrian family with an affected girl having complete alopecia and nail dystrophy since birth. The family clearly showed linkage to chromosome 12q13.13-12q14.3, which excluded the KRT85 gene. Sequencing of another candidate gene HOXC13 within the linkage interval identified a homozygous frameshift mutation (c.355delC; p.Leu119Trpfs*20). Expression studies in cultured cells revealed that the mutant HOXC13 protein mislocalized within the cytoplasm, and failed to upregulate the promoter activities of its target genes. Our results strongly suggest crucial roles of the HOXC13 gene in the development of hair and nails in humans.

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Autosomal recessive pure hair and nail ectodermal dysplasia linked to chromosome 12p11.1-q14.3 without KRTHB5 gene mutation

Cited by 10 publications

References 0 publications

Autosomal Recessive Transmission of a Rare KRT74 Variant Causes Hair and Nail Ectodermal Dysplasia: Allelism with Dominant Woolly Hair/Hypotrichosis

Autosomal Recessive Transmission of a Rare KRT74 Variant Causes Hair and Nail Ectodermal Dysplasia: Allelism with Dominant Woolly Hair/Hypotrichosis

Review of Keratin Disorders

A Homozygous Frameshift Mutation in theHOXC13Gene Underlies Pure Hair and Nail Ectodermal Dysplasia in a Syrian Family

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