Implementation of a gene panel for genetic diagnosis of primary ciliary dyskinesia

Abstract Introduction Primary ciliary dyskinesia (PCD) is characterized by an alteration in the ciliary structure causing difficulty in the clearance of respiratory secretions. Diagnosis is complex and based on a combination of techniques. The objective of this study was to design a gene panel including all known causative genes, and to corroborate their diagnostic utility in a cohort of Spanish patients. Methods This was a multicenter cross-sectional study of patients with a high suspicion of PCD according to European Respiratory Society criteria. We designed a gene panel for massive sequencing using SeqCap EZ capture technology that included 44 genes associated with PCD. Results We includ…

Effects of Omalizumab Treatment in Patients With Recalcitrant Nasal Polyposis and Mild Asthma: A Multicenter Retrospective Study

Background Chronic rhinosinusitis with nasal polyps (CRSwNP) is a clinical entity with specific features that impacts significantly on patient quality of life (QoL). CRSwNP is often associated with asthma and is difficult to control and manage despite pharmacological and/or surgical treatment. Omalizumab, a monoclonal anti-IgE antibody, has emerged as a putative therapeutic option. Objective To evaluate the effects of omalizumab on nasal polyp (NP) size and QoL assessed by Sino-Nasal Outcome Test-22 (SNOT-22) in patients with recalcitrant CRSwNP and mild asthma. Methods A multicenter retrospective analysis of patient data from the Community of Valencia (Spain) was performed. Adult patients …

Axonemal Symmetry Break, a New Ultrastructural Diagnostic Tool for Primary Ciliary Dyskinesia?

Diagnosis testing for primary ciliary dyskinesia (PCD) requires a combination of investigations that includes study of ciliary beat pattern by high-speed video-microscopy, genetic testing and assessment of the ciliary ultrastructure by transmission electron microscopy (TEM). Historically, TEM was considered to be the “gold standard” for the diagnosis of PCD. However, with the advances in molecular genetic techniques, an increasing number of PCD variants show normal ultrastructure and cannot be diagnosed by TEM. During ultrastructural assessment of ciliary biopsies of patients with suspicion of PCD, we observed an axonemal defect not previously described that affects peripheral doublets tilt…

Giant deep lobe parotid tumor removal via total parotidectomy without mandibulotomy. A simple and safe technique

The transmandibular route is often combined with the transparotid-transcervical approach when extensive surgical field exposure is required, as in the case of deep parotid lobe tumors measuring over 4 cm in size. This procedure implies great morbidity and prolongs surgery time. Furthermore, in cases where additional lip division is performed, the aesthetic outcomes may be poorer. A description is made of the technique used for the removal of giant pleomorphic adenomas of the parapharyngeal space, without mandibulotomy. Key words:Parapharyngeal space tumor, pleomorphic adenoma, transcervical-transparotid approach, transmandibular approach.

Implementación de un panel de genes para el diagnóstico genético de la discinesia ciliar primaria

Resumen Introduccion La discinesia ciliar primaria (DCP) es una enfermedad caracterizada por una alteracion en la estructura ciliar que impide el correcto aclaramiento de las secreciones respiratorias. Su diagnostico es complejo y se basa en una combinacion de tecnicas. El objetivo de este estudio fue disenar un panel de genes incluyendo todos los genes causantes conocidos y comprobar su utilidad diagnostica en una cohorte de pacientes espanoles. Metodos Estudio transversal multicentrico de pacientes con sospecha elevada de DCP, aplicando los criterios de la European Respiratory Society. Diseno de un panel de genes para secuenciacion masiva con la tecnologia de captura SeqCap EZ technology,…

Understanding Primary Ciliary Dyskinesia: Experience From a Mediterranean Diagnostic Reference Centre

Background: Due to the lack of a gold standard diagnostic test, reference centres with experienced personnel and costly procedures are needed for primary ciliary dyskinesia (PCD) diagnostics. Diagnostic flowcharts always start with clinical symptoms. Therefore, the aim of this work is to define differential clinical criteria so that only patients clinically compatible with PCD are referred to reference centres. Materials and methods: 18 variables from 476 Mediterranean patients with clinically suspicious PCD were collected. After analysing cilia function and ultrastructure, 89 individuals were diagnosed with PCD and 387 had a negative diagnosis. Simple logistic regression analysis, consider…

New insights in primary ciliary dyskinesia

Introduction: Primary ciliary dyskinesia (PCD) is a rare genetic disease with an estimated prevalence of 1:20.000 births. It is characterized by abnormal motility of cilia, leading to impaired mucociliary clearance, and subsequent infection and chronic inflammation of the airways. PCD also affects spermatozoa and cilia in the Fallopian tubes, contributing to fertility issues; dyskinesia of embryonic nodal cilia causes a random distribution of the organs. Areas covered: An overview of the history, genetics, clinical manifestations in children and adults, diagnostic tests, treatments, and prognosis are reviewed. We also discuss current research and future prospects of PCD. Expert opinion: As …

Immunofluorescence Analysis as a Diagnostic Tool in a Spanish Cohort of Patients with Suspected Primary Ciliary Dyskinesia

Primary ciliary dyskinesia (PCD) is an autosomal recessive rare disease caused by an alteration of ciliary structure. Immunofluorescence, consisting in the detection of the presence and distribution of cilia proteins in human respiratory cells by fluorescence, has been recently proposed as a technique to improve understanding of disease-causing genes and diagnosis rate in PCD. The objective of this study is to determine the accuracy of a panel of four fluorescently labeled antibodies (DNAH5, DNALI1, GAS8 and RSPH4A or RSPH9) as a PCD diagnostic tool in the absence of transmission electron microscopy analysis. The panel was tested in nasal brushing samples of 74 patients with clinical suspic…

Improving the Management of Patients with Hearing Loss by the Implementation of an NGS Panel in Clinical Practice

A cohort of 128 patients from 118 families diagnosed with non-syndromic or syndromic hearing loss (HL) underwent an exhaustive clinical evaluation. Molecular analysis was performed using targeted next-generation sequencing (NGS) with a custom panel that included 59 genes associated with non-syndromic HL or syndromic HL. Variants were prioritized according to the minimum allele frequency and classified according to the American College of Medical Genetics and Genomics guidelines. Variant(s) responsible for the disease were detected in a 40% of families including autosomal recessive (AR), autosomal dominant (AD) and X-linked patterns of inheritance. We identified pathogenic or likely pathogen…

Papel de la inmunofluorescencia y el diagnóstico molecular en la caracterización de la discinesia ciliar primaria

Multicentric recurrent parotid pleomorphic adenoma in a child

Mixed tumours of the parotid gland are rare in childhood and recurrence of this tumour is infrequent. Some authors report a higher rate of recurrence with some histological subtypes, like hypocellular variant. Female sex and young age at initial treatment are also risk factor for recurrence. Also the first surgical treatment, tumour enucleation or parotidectomy, has been implicated as a cause for recurrence. We present a case of a multicentric doubly recurrent parotid pleomorphic adenoma, 7 and 14 years after tumour enucleation, in a 9-year-old child. All the nodules resected showed the hypocellular variant of pleomorphic adenoma. We consider the relationships between the choice of treatmen…

sj-pdf-1-ajr-10.1177_1945892420972326 - Supplemental material for Effects of Omalizumab Treatment in Patients With Recalcitrant Nasal Polyposis and Mild Asthma: A Multicenter Retrospective Study

Supplemental material, sj-pdf-1-ajr-10.1177_1945892420972326 for Effects of Omalizumab Treatment in Patients With Recalcitrant Nasal Polyposis and Mild Asthma: A Multicenter Retrospective Study by Miguel Armengot-Carceller MD, PhD María José Gómez-Gómez MD, PhD Carmen García-Navalón MD Encarna Doménech-Campos Muñoz- Noelia Fernández MD, PhD MD, PhD Ainhoa García-Lliberós de Miguel MD, PhD Jaime Marco-Algarra MD, PhD Marta Palop-Cervera MD Alfonso García Piñero MD, PhD in American Journal of Rhinology & Allergy