0
views
0
recommends
+1 Recommend
0 collections
    0
    shares
      • Record: found
      • Abstract: found
      • Article: found
      Is Open Access

      Congenital Sensorineural Hearing Loss and Inborn Pigmentary Disorders: First Report of Multilocus Syndrome in Piebaldism

      case-report

      Read this article at

      Bookmark
          There is no author summary for this article yet. Authors can add summaries to their articles on ScienceOpen to make them more accessible to a non-specialist audience.

          Abstract

          Congenital sensorineural hearing loss may occur in association with inborn pigmentary defects of the iris, hair, and skin. These conditions, named auditory-pigmentary disorders (APDs), represent extremely heterogeneous hereditary diseases, including Waardenburg syndromes, oculocutaneous albinism, Tietz syndrome, and piebaldism. APDs are part of the neurocristopathies, a group of congenital multisystem disorders caused by an altered development of the neural crest cells, multipotent progenitors of a wide variety of different lineages, including those differentiating into peripheral nervous system glial cells and melanocytes. We report on clinical and genetic findings of two monozygotic twins from a large Albanian family who showed a complex phenotype featured by sensorineural congenital deafness, severe neuropsychiatric impairment, and inborn pigmentary defects of hair and skin. The genetic analyzes identified, in both probands, an unreported co-occurrence of a new heterozygous germline pathogenic variant (c.2484 + 5G > T splicing mutation) in the KIT gene, consistent with the diagnosis of piebaldism, and a heterozygous deletion at chromosome 15q13.3, responsible for the neuropsychiatric impairment. This case represents the first worldwide report of dual locus inherited syndrome in piebald patients affected by a complex auditory-pigmentary multisystem phenotype. Here we also synthesize the clinical and genetic findings of all known neurocristopathies characterized by a hypopigmentary congenital disorder.

          Related collections

          Most cited references19

          • Record: found
          • Abstract: found
          • Article: not found

          Resolution of Disease Phenotypes Resulting from Multilocus Genomic Variation.

          Background Whole-exome sequencing can provide insight into the relationship between observed clinical phenotypes and underlying genotypes. Methods We conducted a retrospective analysis of data from a series of 7374 consecutive unrelated patients who had been referred to a clinical diagnostic laboratory for whole-exome sequencing; our goal was to determine the frequency and clinical characteristics of patients for whom more than one molecular diagnosis was reported. The phenotypic similarity between molecularly diagnosed pairs of diseases was calculated with the use of terms from the Human Phenotype Ontology. Results A molecular diagnosis was rendered for 2076 of 7374 patients (28.2%); among these patients, 101 (4.9%) had diagnoses that involved two or more disease loci. We also analyzed parental samples, when available, and found that de novo variants accounted for 67.8% (61 of 90) of pathogenic variants in autosomal dominant disease genes and 51.7% (15 of 29) of pathogenic variants in X-linked disease genes; both variants were de novo in 44.7% (17 of 38) of patients with two monoallelic variants. Causal copy-number variants were found in 12 patients (11.9%) with multiple diagnoses. Phenotypic similarity scores were significantly lower among patients in whom the phenotype resulted from two distinct mendelian disorders that affected different organ systems (50 patients) than among patients with disorders that had overlapping phenotypic features (30 patients) (median score, 0.21 vs. 0.36; P=1.77×10(-7)). Conclusions In our study, we found multiple molecular diagnoses in 4.9% of cases in which whole-exome sequencing was informative. Our results show that structured clinical ontologies can be used to determine the degree of overlap between two mendelian diseases in the same patient; the diseases can be distinct or overlapping. Distinct disease phenotypes affect different organ systems, whereas overlapping disease phenotypes are more likely to be caused by two genes encoding proteins that interact within the same pathway. (Funded by the National Institutes of Health and the Ting Tsung and Wei Fong Chao Foundation.).
            Bookmark
            • Record: found
            • Abstract: found
            • Article: found

            The neural crest

            The neural crest (NC) is a highly migratory multipotent cell population that forms at the interface between the neuroepithelium and the prospective epidermis of a developing embryo. Following extensive migration throughout the embryo, NC cells eventually settle to differentiate into multiple cell types, ranging from neurons and glial cells of the peripheral nervous system to pigment cells, fibroblasts to smooth muscle cells, and odontoblasts to adipocytes. NC cells migrate in large numbers and their migration is regulated by multiple mechanisms, including chemotaxis, contact-inhibition of locomotion and cell sorting. Here, we provide an overview of NC formation, differentiation and migration, highlighting the molecular mechanisms governing NC migration.
              Bookmark
              • Record: found
              • Abstract: found
              • Article: not found

              Tissue interactions in neural crest cell development and disease.

              The neural crest is a transient population of migratory cells in the embryo that gives rise to a wide variety of different cell types, including those of the peripheral nervous system. Dysfunction of neural crest cells (NCCs) is associated with multiple diseases, such as neuroblastoma and Hirschsprung disease. Recent studies have identified NCC behaviors during their migration and differentiation, with implications for their contributions to development and disease. Here, we describe how interactions between cells of the neural crest and lineages such as the vascular system, as well as those involving environmental signals and microbial pathogens, are critically important in determining the roles played by these cells.
                Bookmark

                Author and article information

                Journal
                Medicina (Kaunas)
                medicina
                Medicina
                MDPI
                1010-660X
                1648-9144
                07 July 2019
                July 2019
                : 55
                : 7
                : 345
                Affiliations
                [1 ]Department of Health Sciences, Amedeo Avogadro University of Eastern Piedmont, 28100 Novara, Italy
                [2 ]Department of Translational Medicine, Amedeo Avogadro University of Eastern Piedmont, 28100 Novara, Italy
                [3 ]Department of Medical Sciences, University of Turin, 10124 Torino, Italy
                [4 ]Medical Genetics Unit, Città della Salute e della Scienza University Hospital, 10124 Torino, Italy
                [5 ]Maternal Infant Department, Castelli Hospital, 28922 Verbania, Italy
                Author notes
                [* ]Correspondence: gironi.laura@ 123456gmail.com ; Tel.: +39-032-1373-3269; Fax: +39-032-1373-3117
                Author information
                https://orcid.org/0000-0002-7298-4446
                https://orcid.org/0000-0002-8318-7231
                https://orcid.org/0000-0002-1636-8411
                Article
                medicina-55-00345
                10.3390/medicina55070345
                6681376
                31284637
                235ab8f8-a2a6-4996-a573-e075937be0f0
                © 2019 by the authors.

                Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license ( http://creativecommons.org/licenses/by/4.0/).

                History
                : 01 April 2019
                : 04 July 2019
                Categories
                Case Report

                genodermatoses,genetic skin disorders,auditory-pigmentary disorders,neurocristopathies,piebaldism,multilocus syndrome,kit,15q13.3 deletion

                Comments

                Comment on this article