Pachyonychia Congenita (K16) with Unusual Features and Good Response to Acitretin

Background: Pachyonychia congenita (PC) is a rare autosomal dominant disease whose main clinical features include hypertrophic onychodystrophy and palmoplantar keratoderma. The new classification is based on genetic variants with mutations in keratin KRT6A, KRT6B, KRT6C, KRT16, KRT17, and an unknown mutation. Here, we present a case of PC with unusual clinical and histological features and a favorable response to oral acitretin. Case: A 49-year-old male presented with diffuse and striate palmoplantar keratoderma, thickened nails, knuckle pads, and pseudoainhum. Histology showed compact hyperkeratosis, prominent irregular acanthosis, and extensive epidermolytic hyperkeratosis, suggestive of Vörner's palmoplantar keratoderma. However, keratin 9 and 1 were not mutated, and full exome sequencing showed heterozygous missense mutation in type I keratin K16. Conclusion: To our knowledge, epidermolytic hyperkeratosis has not been previously described with PC. Our patient had an excellent response, maintained over the last 5 years, to a low dose of acitretin. We wish to emphasize the crucial role of whole exome sequencing in establishing the correct diagnosis.

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Faculty Opinions recommendation of Gene identification in the congenital disorders of glycosylation type I by whole-exome sequencing.

Faculty Opinions – Post-Publication Peer Review of the Biomedical Literature ◽

10.3410/f.717956777.793461365 ◽

2012 ◽

Author(s):

Jane Hewitt

Keyword(s):

Exome Sequencing ◽

Whole Exome Sequencing ◽

Gene Identification ◽

Congenital Disorders ◽

Type I ◽

Congenital Disorders Of Glycosylation ◽

Whole Exome

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Faculty Opinions recommendation of Whole-exome sequencing of 2,000 Danish individuals and the role of rare coding variants in type 2 diabetes.

Faculty Opinions – Post-Publication Peer Review of the Biomedical Literature ◽

10.3410/f.718194747.793488319 ◽

2013 ◽

Author(s):

Alon Keinan

Keyword(s):

Type 2 Diabetes ◽

Exome Sequencing ◽

Whole Exome Sequencing ◽

Whole Exome ◽

Coding Variants

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Exploration of the role of whole exome sequencing variants in -associated Parkinson disease

Molecular Genetics and Metabolism ◽

10.1016/j.ymgme.2020.12.279 ◽

2021 ◽

Vol 132 (2) ◽

pp. S113

Author(s):

Elizabeth Geena Woo ◽

Frank Donovan ◽

Barbara Stubblefield ◽

Settara Chandrasekharappa ◽

Grisel Lopez ◽

...

Keyword(s):

Parkinson Disease ◽

Exome Sequencing ◽

Whole Exome Sequencing ◽

Whole Exome

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Whole Exome Sequencing identifies the potential role of genes involved in p53 pathway in Nasopharyngeal Carcinoma from Northeast India

Gene ◽

10.1016/j.gene.2021.146099 ◽

2021 ◽

pp. 146099

Author(s):

Shaheen Laskar ◽

Raima Das ◽

Sharbadeb Kundu ◽

Amrita Saha ◽

Nilashis Nandi ◽

...

Keyword(s):

Nasopharyngeal Carcinoma ◽

Exome Sequencing ◽

Whole Exome Sequencing ◽

Potential Role ◽

Northeast India ◽

P53 Pathway ◽

Whole Exome

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Identification of a novel causative mutation in KRT1 in diffuse palmoplantar keratoderma, facilitated by whole-exome sequencing

European Journal of Dermatology ◽

10.1684/ejd.2021.4017 ◽

2021 ◽

Vol 31 (2) ◽

pp. 264-265

Author(s):

So Takeuchi ◽

Takuya Takeichi ◽

Yasutoshi Ito ◽

Kana Tanahashi ◽

Yoshinao Muro ◽

...

Keyword(s):

Exome Sequencing ◽

Whole Exome Sequencing ◽

Causative Mutation ◽

Palmoplantar Keratoderma ◽

Whole Exome

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Whole Exome Sequencing Provides the Correct Diagnosis in a Case of Osteopathia Striata with Cranial Sclerosis: Case Report of a Novel Frameshift Mutation in AMER1

Journal of Pediatric Genetics ◽

10.1055/s-0040-1710058 ◽

2020 ◽

Author(s):

José María García-Aznar ◽

Noelia Ramírez ◽

David De Uña ◽

Elisa Santiago ◽

Lorenzo Monserrat

Keyword(s):

Exome Sequencing ◽

Whole Exome Sequencing ◽

Target Genes ◽

Correct Diagnosis ◽

Sotos Syndrome ◽

Pathogenic Variants ◽

Osteopathia Striata ◽

Whole Exome ◽

Cranial Sclerosis ◽

Extended Analysis

AbstractThe diagnosis of rare diseases with multisystem manifestations can constitute a difficult process that delays the determination of the underlying cause. Whole exome sequencing (WES) provides a suitable option to examine multiple target genes associated with several disorders that display common features. In this study, we report the case of a female patient suspected of having Sotos syndrome. Screening for the initially selected genes, considering Sotos syndrome and Sotos-like disorders, did not identify any pathogenic variants that could explain the phenotype. The extended analysis, which considered all genes in the exome associated with features consistent with those shown by the studied patient, revealed a novel frameshift variant in the AMER1 gene, responsible for osteopathia striata with cranial sclerosis. WES analysis and an updated revision of previously reported disease-causing mutations, proved useful to reach an accurate diagnosis and guide further examination to identify critical abnormalities.

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Identification of a Heterozygous Mutation in the TGFBI Gene in a Hui-Chinese Family with Corneal Dystrophy

Journal of Ophthalmology ◽

10.1155/2019/2824179 ◽

2019 ◽

Vol 2019 ◽

pp. 1-7 ◽

Cited By ~ 1

Author(s):

Qin Xiang ◽

Lamei Yuan ◽

Yanna Cao ◽

Hongbo Xu ◽

Yunfeiyang Li ◽

...

Keyword(s):

Exome Sequencing ◽

Whole Exome Sequencing ◽

Sanger Sequencing ◽

Transforming Growth Factor ◽

Corneal Dystrophy ◽

Chinese Family ◽

Heterozygous Mutation ◽

Type I ◽

Whole Exome ◽

The Family

Background/Aims. Corneal dystrophies (CDs) belong to a group of hereditary heterogeneous corneal diseases which result in visual impairment due to the progressive accumulation of deposits in different corneal layers. So far, mutations in several genes have been responsible for various CDs. The purpose of this study is to identify gene mutations in a three-generation Hui-Chinese family associated with granular corneal dystrophy type I (GCD1). Methods. A three-generation Hui-Chinese pedigree with GCD1 was recruited for this study. Slit-lamp biomicroscopy, optical coherence tomography, and confocal microscopy were performed to determine the clinical features of available members. Whole exome sequencing was performed on two patients to screen for potential disease-causing variants in the family. Sanger sequencing was used to test the variant in the family members. Results. Clinical examinations demonstrated bilaterally abundant multiple grayish-white opacities in the basal epithelial and superficial stroma layers of corneas of the two patients. Whole exome sequencing revealed that a heterozygous missense mutation (c.1663C > T, p.Arg555Trp) in the transforming growth factor beta-induced gene (TGFBI) was shared by the two patients, and it cosegregated with this disease in the family confirmed by Sanger sequencing. Conclusions. The results suggested that the heterozygous TGFBI c.1663C > T (p.Arg555Trp) mutation was responsible for GCD1 in the Hui-Chinese family, which should be of great help in genetic counseling for this family.

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Investigation of the role of vitamin D metabolism in South African breast cancer patients using whole exome sequencing

The Breast ◽

10.1016/s0960-9776(19)30162-6 ◽

2019 ◽

Vol 44 ◽

pp. S36

Author(s):

A. Okunola ◽

R. Torrorey-Sawe ◽

K.J. Baatjes ◽

A.E. Zemlin ◽

R.T. Erasmus ◽

...

Keyword(s):

Breast Cancer ◽

Vitamin D ◽

Exome Sequencing ◽

Cancer Patients ◽

South African ◽

Whole Exome Sequencing ◽

Breast Cancer Patients ◽

Vitamin D Metabolism ◽

Whole Exome

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Chiari 1 malformation and exome sequencing in 51 trios: the emerging role of rare missense variants in chromatin-remodeling genes

Human Genetics ◽

10.1007/s00439-020-02231-6 ◽

2020 ◽

Author(s):

Aldesia Provenzano ◽

Andrea La Barbera ◽

Mirko Scagnet ◽

Angelica Pagliazzi ◽

Giovanna Traficante ◽

...

Keyword(s):

Exome Sequencing ◽

Chromatin Remodeling ◽

Brain Mri ◽

Cranial Bone ◽

Genetic Syndromes ◽

Whole Exome ◽

Cerebellar Tonsillar Herniation ◽

Brain Magnetic Resonance Image

AbstractType 1 Chiari malformation (C1M) is characterized by cerebellar tonsillar herniation of 3–5 mm or more, the frequency of which is presumably much higher than one in 1000 births, as previously believed. Its etiology remains undefined, although a genetic basis is strongly supported by C1M presence in numerous genetic syndromes associated with different genes. Whole-exome sequencing (WES) in 51 between isolated and syndromic pediatric cases and their relatives was performed after confirmation of the defect by brain magnetic resonance image (MRI). Moreover, in all the cases showing an inherited candidate variant, brain MRI was performed in both parents and not only in the carrier one to investigate whether the defect segregated with the variant. More than half of the variants were Missense and belonged to the same chromatin-remodeling genes whose protein truncation variants are associated with severe neurodevelopmental syndromes. In the remaining cases, variants have been detected in genes with a role in cranial bone sutures, microcephaly, neural tube defects, and RASopathy. This study shows that the frequency of C1M is widely underestimated, in fact many of the variants, in particular those in the chromatin-remodeling genes, were inherited from a parent with C1M, either asymptomatic or with mild symptoms. In addition, C1M is a Mendelian trait, in most cases inherited as dominant. Finally, we demonstrate that modifications of the genes that regulate chromatin architecture can cause localized anatomical alterations, with symptoms of varying degrees.

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