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Clinical findings in ectodermal dysplasia. ( a ) Clinical presentation of abnormal scalp hair of individual V-6 at 20 y of age ( b ) highly dystrophic fingernails of individual V-6 ( top ). Toenails of the same individual show- ing anonychia ( bottom ).
Source publication
Ectodermal dysplasia (ED) represents a heterogeneous group of genetic disorders characterized by the absence or deformity in two or more of the ectodermal appendages. We have studied an autosomal recessive form of ED in 13 individuals over six generations from an inbred Pakistani family. The clinical features of the affected individuals include hig...
Contexts in source publication
Context 1
... of the affected individuals underwent examination at Department of Dermatology, Pakistan Institute of Medical Sciences, Islamabad. The affected individuals had thin scalp hair (Fig 3a), fine eyebrows and eyelashes, and thin body hair. Nail alteration were mostly present since birth in all digits and soon reached an individually variable degree of severity. ...
Context 2
... alteration were mostly present since birth in all digits and soon reached an individually variable degree of severity. The fingernails exhibited micronychia, resulting in dystrophic appearance, and toenails were completely absent (anonychia) in all the affected subjects (Fig 3b). Patients showed no alteration of dentition, no malfunction of sweat glands, and no skeletal abnormalities. ...
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Citations
... 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 ...
Background: Pure 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. Methods: In 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.
... 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 ...
Background
Pure 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.
Methods
In 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.
Results
Through 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.
Conclusion
This is the first mutation reported in homeodomain, while 5th mutation reported in HOXC13 gene causing PHNED.
... 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 ...
Background: Pure 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.
Methods: In 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.
Results: Through 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.
Conclusion: This is the first mutation reported in homeodomain, while 5th mutation reported in HOXC13 gene
causing PHNED.
... However, mutations in one gene cause clinically different EDs and mutations in different genes can determine the same ED entity, as will be discussed. Two conditions (Table III) for which only the clinical subgroups and chromosomal regions were assigned [Rafiq et al., 2005;Tariq et al., 2008] were not included in Table I, as they may represent previously described EDs. ...
Ectodermal dysplasias (EDs) as defined by Freire-Maia [Freire-Maia (1971); Hum Hered 21: 309-312; Freire-Maia (1977); Acta Genet Med Gemellol 26: 121-131] are congenital disorders characterized by alterations in two or more ectodermal structures, at least one of these involving alterations in hair, teeth, nails, or sweat glands. Suggestions for a new definition and, consequently, for a new classification of EDs have being proposed lately, mainly with the purpose of connecting clinical knowledge with recent discoveries of gene mutations responsible for about 30% of EDs. The aim of this review was to update the clinical classification of EDs with recent molecular (64 genes and 3 chromosome regions) and clinical data, mainly of EDs of the A group (N = 186), in order to contribute information for the evaluation of the ED definition proposed by Freire-Maia. Our conclusion is that the combination of both procedures-clinical and molecular-only brings advantages for a deeper knowledge of EDs. First, it allows a rapid diagnosis that may become even more precise whenever DNA exams are available. Secondly, the comprehension of the biological mechanisms that cause EDs is needed for the design of efficient prevention and treatment approaches.
... Hair and nail type Ectodermal dysplasia (MIM 602032) is a disorder characterized by alopecia and dystrophy of the finger-and toe-nails (Barbareschi et al. 1997;Harrison & Sinclair, 2004). Recently, three autosomal recessive forms of ED of the pure hair and nail type were mapped to chromosomes 10q24.32-q25.1 (Rafiq et al. 2005), 12q13.13 (Naeem et al. 2006a) and 17q12-q21.2 ...
Ectodermal dysplasias (EDs) are developmental disorders affecting tissues of ectodermal origin including hair, nails, teeth and sweat glands. Ectodermal dysplasia of hair, nails and teeth is a rare type of congenital disorder characterized by sparse and thin hair, dystrophic finger-and toenails and missing and abnormal teeth. In an effort to understand the molecular basis of this form of ED a family of Pakistani origin with an autosomal recessive pattern of inheritance was ascertained from a remote region in Pakistan. The clinical features of the affected individuals included thin and fine hair on the scalp, dystrophic and flat nails, absent or sparse eyebrows and eyelashes, missing and abnormal teeth, and thin body hair. A human genome scan carried out using microsatellite markers mapped the disease locus in this family to chromosome 18q22.1-18q22.3. A maximum two-point LOD score of 2.73 (theta= 0.0) was obtained at marker D18S541. Multipoint linkage analysis resulted in a maximum LOD score of 3.42 obtained with several markers, including D18S1125, ATA82B02, D18S848, D18S488, D18S1091, and D18S485, which supported the linkage. The linkage interval is flanked by markers D18S857 and D18S815, which corresponds to a region of 17.32 cM according to Rutgers combined linkage and physical map (build 36). This region covers 8.63 Mb according to the sequence-based physical map. Three candidate genes, CDH7, CDH19 and ZNF407, from the linkage interval were sequenced and found to be negative for functional sequence variants. This study is the first step towards the identification of a gene involved in hair, nails and teeth type ED.
... An autosomal recessive form of pure hair and nail ED was described in a Pakistani family of 13 affected individuals. 6 The patients had thin scalp and body hair and fine eyebrows and eyelashes. Nail dystrophy was present in all digits. ...
Ectodermal dysplasias (EDs) describe a large and complex group of disorders characterized by abnormal development of the skin and appendages (hair, nails, teeth and sweat glands). Of the approximately 200 different EDs, about 30 have been studied at the molecular level. In an effort to understand the molecular bases of ED of hair and nail type, we studied a Pakistani consanguineous family with multiple affected individuals.
To localize the gene responsible for the autosomal recessive form of ED of hair and nail type.
Genotyping of nine members of the family, including five affected and four normal individuals was performed using microsatellite markers mapping to candidate regions, harbouring genes involved in related phenotypes. Five epithelial keratin genes located in the candidate region were sequenced to identify the pathogenic mutation.
We mapped the disease locus to a 24.2-cM interval flanked by markers D17S839 and D17S1299 on chromosome 17p12-q21.2 (Z(max) = 4.4). DNA sequencing of five epithelial keratin candidate genes, present in the disease locus, did not reveal any pathogenic mutation in the affected individuals.
The gene for ED of hair and nail type has been mapped to chromosome 17p12-q21.2 in a Pakistani consanguineous family. Failure to detect mutations in epithelial keratin genes suggests that the mutation may lie either in regulatory regions of one of the epithelial keratin genes or in another unknown gene, located in the linkage interval, with a possible role in the development of ectodermal appendages.
Pure hair and nail ectodermal dysplasia (PHNED) is a rare disorder that presents with hypotrichosis and nail dystrophy while sparing other ectodermal structures such as teeth and sweat glands. We describe a homozygous novel missense mutation in the HOXC13 gene that resulted in autosomal recessive PHNED in a Hispanic child. The mutation c.812A>G (p.Gln271Arg) is located within the DNA-binding domain of the HOXC13 gene, cosegregates within the family, and is predicted to be maximally damaging. This is the first reported case of a missense HOXC13 mutation resulting in PHNED and the first reported case of PHNED identified in a North American family. Our findings illustrate the critical role of HOXC13 in human hair and nail development.
Abstract
Ectodermal dysplasias (ED) are a rare group of genodermatoses affecting
tissues of ectodermal origin namely: hair, nails, teeth, and sweat glands. Pure
hair, nail ectodermal dysplasias (PHNED) are very rare, and involve only hair
and nails, while other ectodermal structures are intact. To date only 20 cases
have been reported in the world literature. We report two cases of PHNED in
a 15 years old Yemeni boy, and his 2 months old sister, who were born with
total absence of hairs and dystrophic 20 nails. All other family members were
not affected.
Ectodermal dysplasia is a rare congenital disease that affects the ectodermal structures. It is characterized by hypotrichosis, hypohidrosis and hypodontia. A 14-year-old boy with ectodermal dysplasia presenting with oligodontia and marked resorption of the maxillary and mandibular alveolar ridges is reported. Prosthetic rehabilitation in the form of a maxillary and mandibular partial denture was made with metal crowns on existing lower teeth to achieve appropriate vertical dimension. Significant improvement in speech, masticatory function and facial esthetics was achieved. Removable prosthodontics can provide an acceptable solution to esthetic, functional and psychological rehabilitation in patients with ectodermal dysplasia.
Ectodermal dysplasias (ED) are developmental disorders affecting tissues of ectodermal origin including hair, nail, teeth and sweat glands. To date, four different types of ectodermal dysplasias involving only hair and nails have been described. In an effort to understand the molecular basis of ED of hair and nails, a Pakistani family with multiple affected individuals was studied. Linkage analysis was carried out by genotyping eight members of the family (five normal and three affected) using microsatellite markers linked to the related phenotype. The diseased phenotype was mapped to chromosome 12p11.1-q21.1 (Zmax=3.1). DNA sequence analysis of the coding exons and splice sites of six hair keratin genes, located in the linkage interval, failed to detect any pathogenic mutation in the affected individuals of the family. Failure to detect a mutation in the epithelial keratin genes suggests that the mutation lies either in the regulatory region of one of the keratin genes or in another unknown gene, located in the linkage interval, with a possible role in the development of ectodermal appendages.
