Pili torti and Onychodysplasia

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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“…Inheritance mode of PHNED is both autosomal recessive and dominant [1, 2]. No gene has been reported for autosomal dominant PHNED.…”

Section: Introductionmentioning

confidence: 99%

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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“…1,2 Pure hair and nail ectodermal dysplasia (PHNED [MIM 602032]) is a rare congenital condition characterized by hypotrichosis and nail dystrophy without nonectodermal or other ectodermal manifestations. 3 Hypotrichosis usually occurs after birth with varying degrees of severity, ranging from mild hair loss to complete atrichia, including the loss of scalp hair, beard, eyebrows, eyelashes, axillary hair, and pubic hair. Nail dystrophy affects all twenty digits by causing short fragile nails or spoon nails (koilonychias).…”

mentioning

confidence: 99%

“…Nail dystrophy affects all twenty digits by causing short fragile nails or spoon nails (koilonychias). At least five clinical forms of PHNED with unique manifestations have been described [3][4][5][6][7][8] with either autosomal-recessive or autosomal-dominant patterns of inheritance. In 2006, Naeem and colleagues performed linkage analysis in a consanguineous Pakistani family affected by PHNED and mapped the locus to chromosomal region 12q12-q14.1, which contains the type II hair keratin and HOXC gene clusters.…”

mentioning

confidence: 99%

Loss-of-Function Mutations in HOXC13 Cause Pure Hair and Nail Ectodermal Dysplasia

Lin

Chen

Shi

et al. 2012

The American Journal of Human Genetics

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Pure hair and nail ectodermal dysplasia (PHNED) is a congenital condition characterized by hypotrichosis and nail dystrophy. Autosomal-recessive PHNED has previously been mapped to chromosomal region 12q12-q14.1, which contains the type II hair keratin and HOXC clusters. Hoxc13-null mice are known to develop hair and nail defects very similar to those seen in human PHNED. We performed whole-exome sequencing in a consanguineous Chinese family affected by PHNED and identified a homozygous nonsense mutation (c.390C>A [p.Tyr130(∗)]) in HOXC13 in all affected individuals. In an additional affected female from a consanguineous Afghan family, we found a 27.6 kb homozygous microdeletion involving the first exon of HOXC13. We examined HOXC13 expression in scalp specimen obtained from the index individual of the Chinese family and detected dramatically reduced mRNA levels in skin tissue and nearly absent protein staining in hair follicles, suggesting a mechanism of nonsense-mediated mRNA decay. We also observed markedly decreased expression of four HOXC13 target genes in the specimen. Taken together, our results demonstrate that loss-of-function mutations in HOXC13 cause autosomal-recessive PHNED and further highlight the importance of HOXC13 in hair and nail development.

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Family with “pure” hair-nail ectodermal dysplasia

et al. 1997

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"Pure" ectodermal dysplasias are developmental disorders affecting only tissues of ectodermal origin. Two different pure ectodermal dysplasias involving only hair and nails have been described to date. Here we describe congenital nail dystrophy and hypotrichosis associated with folliculitis decalvans in a family suggesting autosomal-dominant transmission. This report documents peculiar clinical and ultrastructural hair findings that fit poorly into previously described conditions. Thus the reported patients could represent a new type of pure ectodermal dysplasia.

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Pili torti and Onychodysplasia

Cited by 34 publications

References 10 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

Loss-of-Function Mutations in HOXC13 Cause Pure Hair and Nail Ectodermal Dysplasia

Family with “pure” hair-nail ectodermal dysplasia

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