Novel mutations in the gene<i>HOXC13</i>underlying pure hair and nail ectodermal dysplasia in consanguineous families

Ali, Raheel; Habib, Rabia; Uddin, Naseem; Khan, M. Fahim; Ansar, Muhammad; Ahmad, Wasim

doi:10.1111/bjd.12302

Cited by 17 publications

(20 citation statements)

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“…Clinical features of affected individuals observed in the present family is mostly similar to those reported earlier in ECTD9 families [7–9]. All affected members have complete hair loss and nail dysplasias.…”

Section: Discussionsupporting

confidence: 85%

“…All the three affected members showed homozygosity with several markers (D12S1604, D12S325, D12S1724, D12S1632, D12S1298) linked to Keratin and HOXC genes cluster located on chromosome 12p11.1–q21.1. Three different genes ( KRT74 , KRT85 , HOXC13 ) have been reported in the linked region to be responsible for PHNED [3, 6, 9]. …”

Section: Resultsmentioning

confidence: 99%

“…All affected members have complete hair loss and nail dysplasias. To date, five mutations (Tyr130*, Leu119Trpfs∗20, His68Glnfs*84, Ser135*, 27.6 kb deletion) have been reported in this gene causing PHNED [7–9], of these two mutations have been reported in Pakistani families [http://pakmutation.com/nonsyndromicsearch.aspx]. Based on genotyping and subsequently Sanger sequencing data, we identified a novel mutation (c.929A > C; p.Asn310Thr) in HOXC13 gene.…”

Section: Discussionmentioning

confidence: 99%

“…Based on OMIM classification, there are five autosomal recessive pure hair and nail ectodermal dysplasia types have been reported. These includes ectodermal dysplasia hair and nail type 4 (ECTD4; MIM 602032) lying on chromosome 12q13.13 with mutations in KRT85 gene [3], ectodermal dysplasia hair and nail type 5 (ECTD5; MIM 614927) located on chromosome 10q24.32-q25.1 [4], ectodermal dysplasia hair and nail type 6 (ECTD6; MIM 614928) with chromosomal address 17p12-q21.2 [5], ectodermal dysplasia hair and nail type 7 (ECTD7; MM 614929) lying on chromosome 12q13.13 with mutation in KRT74 gene [6] and ectodermal dysplasia hair and nail type 9 (ECTD9; MIM 614931) harboring HOXC13 gene on chromosome 12q13.13 [7–9]. …”

Section: Introductionmentioning

confidence: 99%

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A novel mutation in homeobox DNA binding domain of HOXC13 gene underlies pure hair and nail ectodermal dysplasia (ECTD9) in a Pakistani family

et al. 2017

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BackgroundPure hair and nail ectodermal dysplasia (PHNED) is a congenital disorder of hair abnormalities and nail dysplasia. Both autosomal recessive and dominant inheritance fashion of PHNED occurs. In literature, to date, five different forms of PHNED have been reported at molecular level, having three genes known and two loci with no gene yet.MethodsIn this study, a four generations consanguineous family of Pakistani origin with autosomal recessive PHNED was investigated. Affected members exhibited PHNED phenotypes with involvement of complete hair loss and nail dysplasia. To screen for mutation in the genes (HOXC13, KRT74, KRT85), its coding exons and exons-intron boundaries were sequenced. The 3D models of normal and mutated HOXC13 were predicted by using homology modeling.ResultsThrough investigating the family to known loci, the family was mapped to ectodermal dysplasia 9 (ECTD9) loci with genetic address of 12q13.13. Mutation screening revealed a novel missense mutation (c.929A > C; p.Asn310Thr) in homeobox DNA binding domain of HOXC13 gene in affected members of the family. Due to mutation, loss of hydrogen bonding and difference in potential energy occurs, which may resulting in alteration of protein function.ConclusionThis is the first mutation reported in homeodomain, while 5th mutation reported in HOXC13 gene causing PHNED.

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Section: Discussionsupporting

confidence: 85%

Section: Resultsmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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A novel mutation in homeobox DNA binding domain of HOXC13 gene underlies pure hair and nail ectodermal dysplasia (ECTD9) in a Pakistani family

et al. 2017

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“…Hoxc13 was reported to be highly expressed in the tail, limbs, and nails in early embryos (95)(96)(97). Hoxc13 deficiency in mice and humans causes external hair loss and nail defects, whereas overexpression of Hoxc13 in mice results in ulceration and alopecia (95)(96)(97)(98)(99)(100). Our studies showed that both HOXA1 and HOXC13 play important roles in YAP-regulated epithelial progenitor cell proliferation.…”

Section: Discussionmentioning

confidence: 66%

YAP Regulates the Expression of Hoxa1 and Hoxc13 in Mouse and Human Oral and Skin Epithelial Tissues

Liu

Zhao

Lin

et al. 2015

Molecular and Cellular Biology

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c Yes-associated protein (YAP) is a Hippo signaling transcriptional coactivator that plays pivotal roles in stem cell proliferation, organ size control, and tumor development. The downstream targets of YAP have been shown to be highly context dependent. In this study, we used the embryonic mouse tooth germ as a tool to search for the downstream targets of YAP in ectoderm-derived tissues. Yap deficiency in the dental epithelium resulted in a small tooth germ with reduced epithelial cell proliferation. We compared the gene expression profiles of embryonic day 14.5 (E14.5) Yap conditional knockout and YAP transgenic mouse tooth germs using transcriptome sequencing (RNA-Seq) and further confirmed the differentially expressed genes using real-time PCR and in situ hybridization. We found that YAP regulates the expression of Hoxa1 and Hoxc13 in oral and dental epithelial tissues as well as in the epidermis of skin during embryonic and adult stages. Sphere formation assay suggested that Hoxa1 and Hoxc13 are functionally involved in YAP-regulated epithelial progenitor cell proliferation, and chromatin immunoprecipitation (ChIP) assay implies that YAP may regulate Hoxa1 and Hoxc13 expression through TEAD transcription factors. These results provide mechanistic insights into abnormal YAP activities in mice and humans. Y es-associated protein (YAP) is a key transcriptional coactivator of the Hippo signaling pathway that plays pivotal roles in stem/progenitor cell proliferation and organ size control (1-11). YAP has also been shown to be a candidate oncogene in the development and progression of multiple human cancers (12-14). The activity of YAP is negatively regulated by its upstream kinase cascade (MstI/2, Sav1, Lats1/2, and Mob1), which leads to the phosphorylation and subsequent degradation of YAP and its paralog TAZ. Inhibition of Hippo signaling relieves YAP and TAZ, which can then translocate into the nucleus. In the nucleus, YAP or TAZ associates with TEAD or other transcription factors to activate the transcription of its target genes (15-18). Conventional knockout of Yap in mice causes early embryonic lethality due to defects in yolk sac vasculogenesis (19). Overexpression of YAP results in enlarged organ size in Drosophila and in mice with profound cell proliferation and inhibition of apoptosis (1,2,7,11, 20). In addition, YAP also plays a critical role in maintaining mouse embryonic stem cell pluripotency and regulating tissue-specific progenitor cells (21).Although the core components of the Hippo pathway are highly conserved between Drosophila and mammalian systems, the transcriptional outputs differ greatly depending on when and where the pathway is deployed. For example, overexpression of YAP in the mouse small intestine leads to Notch-dependent hyperplasia and loss of terminally differentiated cell types but does not appreciably increase the overall size of the organ (1). In Drosophila, the YAP ortholog Yki induces the expression of cycE, diap1, and bantam microRNA (11, 22). In mammalian cells, YAP induces ...

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Skin, Hair, and Nails

Sundberg¹,

King²,

Kuiper³

2021

Pathology of Genetically Engineered and Other Mutant Mice

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Novel mutations in the geneHOXC13underlying pure hair and nail ectodermal dysplasia in consanguineous families

Cited by 17 publications

References 9 publications

A novel mutation in homeobox DNA binding domain of HOXC13 gene underlies pure hair and nail ectodermal dysplasia (ECTD9) in a Pakistani family

A novel mutation in homeobox DNA binding domain of HOXC13 gene underlies pure hair and nail ectodermal dysplasia (ECTD9) in a Pakistani family

YAP Regulates the Expression of Hoxa1 and Hoxc13 in Mouse and Human Oral and Skin Epithelial Tissues

Skin, Hair, and Nails

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