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Isolated recessive nail dysplasia caused by FZD6 mutations: report of three families and review of the literature.

ABSTRACT: Congenital abnormalities of the nail are rare conditions that are most frequently associated with congenital ectodermal syndromes involving several of the epidermal appendages including the skin, teeth, hair and nails. Isolated recessive nail dysplasia (IRND) is much rarer but has recently been recognized as a condition resulting in 20-nail dystrophy in the absence of other cutaneous or extracutaneous findings. A few case reports have identified mutations in the Frizzled 6 (FZD6) gene in families presenting with abnormal nails consistent with IRND. These reports have highlighted the role of Wnt-FZD signalling in the process of nail formation. We report three families presenting with features of IRND, in whom we identified mutations in FZD6, including one previously unreported mutation.

SUBMITTER: Kasparis C

PROVIDER: S-EPMC5132090 | biostudies-literature | 2016 Dec

REPOSITORIES: biostudies-literature

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Isolated recessive nail dysplasia caused by FZD6 mutations: report of three families and review of the literature.

Kasparis C C Reid D D Wilson N J NJ Okur V V Cole C C Hansen C D CD Bosse K K Betz R C RC Khan M M Smith F J D FJ

Clinical and experimental dermatology 20161027 8

Congenital abnormalities of the nail are rare conditions that are most frequently associated with congenital ectodermal syndromes involving several of the epidermal appendages including the skin, teeth, hair and nails. Isolated recessive nail dysplasia (IRND) is much rarer but has recently been recognized as a condition resulting in 20-nail dystrophy in the absence of other cutaneous or extracutaneous findings. A few case reports have identified mutations in the Frizzled 6 (FZD6) gene in familie ...[more]

PMID: 27786367

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A possible founder mutation in FZD6 gene in a Turkish family with autosomal recessive nail dysplasia.

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| S-EPMC6332616 | biostudies-literature

Mutations in Frizzled 6 cause isolated autosomal-recessive nail dysplasia.

Project description:Inherited and isolated nail malformations are rare and heterogeneous conditions. We identified two consanguineous pedigrees in which some family members were affected by isolated nail dysplasia that suggested an autosomal-recessive inheritance pattern and was characterized by claw-shaped nails, onychauxis, and onycholysis. Genome-wide SNP array analysis of affected individuals from both families showed an overlapping and homozygous region of 800 kb on the long arm of chromosome 8. The candidate region spans eight genes, and DNA sequence analysis revealed homozygous nonsense and missense mutations in FZD(6), the gene encoding Frizzled 6. FZD(6) belongs to a family of highly conserved membrane-bound WNT receptors involved in developmental processes and differentiation through several signaling pathways. We expressed the FZD(6) missense mutation and observed a quantitative shift in subcellular distribution from the plasma membrane to the lysosomes, where the receptor is inaccessible for signaling and presumably degraded. Analysis of human fibroblasts homozygous for the nonsense mutation showed an aberrant response to both WNT-3A and WNT-5A stimulation; this response was consistent with an effect on both canonical and noncanonical WNT-FZD signaling. A detailed analysis of the Fzd(6)(-/-) mice, previously shown to have an altered hair pattern, showed malformed claws predominantly of the hind limbs. Furthermore, a transient Fdz6 mRNA expression was observed in the epidermis of the digital tips at embryonic day 16.5 during early claw morphogenesis. Thus, our combined results show that FZD6 mutations can result in severe defects in nail and claw formation through reduced or abolished membranous FZD(6) levels and several nonfunctional WNT-FZD pathways.

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Vitiligo, alkaptonuria, and nitisinone-A report of three families and review of the literature.

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| S-EPMC8411108 | biostudies-literature

Respiratory manifestation of yellow nail syndrome: a case report and literature review.

Project description:Yellow nail syndrome (YNS) is a rare disorder, and diagnosis is based on the clinical findings and the exclusion of other possible causes; the pathogenesis is poorly understood. YNS can be an isolated condition or associated with other diseases; however, YNS associated with multiple myeloma (MM) is rare. A 53-year-old male patient presented with coughing and shortness of breath, and he was diagnosed with YNS with MM. He underwent chemotherapy and achieved a good response. Although the etiology of YNS remains unknown, treating the underlying disease may help prevent or relieve the clinical signs.

| S-EPMC8670787 | biostudies-literature

Cleidocranial dysplasia: case report of three siblings.

Project description:BackgroundA family case report of cleidocranial dysplasia (CCD) with varied manifestations from father to three siblings is presented. CCD ( MIM # 119600) is a rare autosomal dominant skeletal dysplasia caused by CBAF1 gene ( OMIM 600211) with a wide range of variability. In all the cases generalized dysplasia in bone, prolonged retention of primary teeth and delayed eruption of permanent teeth were evident. Interestingly, there were no supernumerary teeth present. There was mandibular prognathism which was intercepted by occipital chin cup therapy.Aims and objectiveTo present the clinical manifestations, diagnostic imaging and treatment modalities along with dermatoglyphics in CCD patients.ConclusionCleidocranial dysplasia is an uncommon disorder however its clinical and radiological features are characteristic. In addition the CCD patients may be distinguished by specific dermatoglyphic markers. It carries with it several implications in terms of complications like skeletal malocclusion, dental caries, etc. Medical treatment is mainly directed at orthopedic and dental correction. A team approach to the management of dental abnormalities on a long-term basis with the overall goal to provide an esthetic facial appearance and functioning occlusion by late adolescence or early adulthood should be focused.

| S-EPMC4086567 | biostudies-literature

Hemoptysis caused by Parvimonas micra: case report and literature review

Project description:Hemoptysis caused by Parvimonas micra: case report and literature review

| PRJEB72347 | ENA

Autosomal recessive transmission of a rare KRT74 variant causes hair and nail ectodermal dysplasia: allelism with dominant woolly hair/hypotrichosis.

Project description: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.

| S-EPMC3979697 | biostudies-literature

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| S-EPMC9108761 | biostudies-literature

Case Report and Review of Literature: Autosomal Recessive Hypophosphatemic Rickets Type 2 Caused by a Pathogenic Variant in <i>ENPP1</i> Gene.

Project description:Autosomal recessive hypophosphatemic rickets type 2 (ARHR2) is a rare form of hereditary rickets, which is characterized by defective bone mineralization and renal phosphate wasting due to a loss-of-function variant in the ectonucleotide pyrophosphatase/phosphodiesterase 1 (ENPP1) gene. Although pathogenic variant of ENPP1 has been known to manifest other phenotypes including arterial calcification, hearing loss, ossification of posterior longitudinal ligament, or pseudoxanthoma elasticum, there have been few reports including systematic examination in individuals diagnosed with ARHR2 to date. Herein, we report a case of ARHR2 with a bi-allelic pathogenic variant of ENPP1, in which the patient presented with gait abnormalities with severe genu varum at 26 months of age. Targeted gene panel sequencing was performed to investigate the genetic cause of rickets, and a homozygous nonsense variant in ENPP1, c.783C>G (p.Tyr261*), was identified. The patient was treated with oral phosphate and active vitamin D supplements and underwent corrective osteotomy for varus deformity. His phenotype was limited to rickets. A periodic systematic evaluation is needed to identify any comorbidities in ARHR2 patients since ENPP1 variants may present phenotypes other than rickets and symptoms may evolve or change over time.

| S-EPMC9374118 | biostudies-literature

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