Monogenic diseases in respiratory medicine: Clinical perspectives

Abstract

With the increasing awareness of genetics in respiratory medicine and improvements in molecular diagnostic techniques, many complicated and rare diseases in respiratory medicine can be diagnosed. Most respiratory diseases have no specific phenotype. However, the clinical spectrum of monogenic diseases in respiratory medicine varies, from pulmonary disease to other inherited disorders that involve the lung. The genes that mediate some of these diseases have been identified. Certain monogenic diseases remain poorly characterized clinically. Because of the specificity of the phenotype of respiratory disease, a future challenge will be to correlate the phenotype and genotype and understand its phenotypic variability. With the development of precision medicine, research on monogenic disorders has been intensive and vigorous. In this article, we provide a brief clinical introduction to monogenic diseases in pediatrics.

Exome sequencing as the first‐tier test for pediatric respiratory diseases: A single‐center study

“…In our cohort, the patients with the following clinical presentation are usually considered to be appropriate for genetic testing: (i) family members with similar symptoms or suspected inheritance diseases; (ii) specific or severe clinical phenotype; (iii) multiple deformities; and (iv) exclusion of other factors (Boycott et al, 2015; Yao & Shen, 2017). Except for certain syndromes with respiratory system involvement, the majority of rare monogenic diseases are often difficult to be recognized by respiratory clinicians due to the short‐term practice of medical genetics in China.…”

“…Nevertheless, advances in sequencing techniques and the knowledge of genetics and genomics have already promoted the applications of NGS in monogenic respiratory disorders, such as primary immunodeficiency disease (PIDs) and primary ciliary dyskinesia (PCD) (Arts et al, 2019; Cifaldi et al, 2019; Fassad et al, 2020; Marshall et al, 2015; Rudilla et al, 2019). Mendelian disorders in respiratory medicine mainly consist of the following three categories: (i) pulmonary disorders, including airway disease, pulmonary parenchymal disease, and pulmonary vascular disease; (ii) sleep disorder; (iii) other monogenic diseases with respiratory system involvement, including PIDs, neuromuscular diseases, and inherited metabolic disease (Yao & Shen, 2017). The clinical manifestation of a majority of monogenic respiratory disorders is often nonspecific and overlaps with other common respiratory diseases, including cough, asthma, pneumonia, bronchitis, bronchopneumonia, and bronchiectasis.…”

Will Airway Gene Therapy for Cystic Fibrosis Improve Lung Function? New Imaging Technologies Can Help Us Find Out

“…1 The exact number of monogenic diseases that affect the respiratory system remains unknown, but two of these-primary ciliary dyskinesia and cystic fibrosis (CF)-are relatively well characterized. 2 It is expected that with success in treating the monogenic diseases, more genetically and/or physiologically complex diseases, such as asthma, allergy, lung cancer, some infections, transplant rejection, and lung injury, will all likely become targets for gene therapy in the future. 3 The most common and life-shortening inherited disease for which genetic treatments are being developed is CF.…”