A novel genetic variant in DNAI2 detected by custom gene panel in a newborn with Primary Ciliary Dyskinesia: case report

BMC Medical Genetics

Carlo Foresta¹  Cinzia Vinanzi¹  Maria Santa Rocca¹  Angelo Valetto²  Veronica Bertini²  Angela Michelucci³  Maria Adelaide Caligo³  Gioia Piatti⁴  Raffaella Guazzo⁵ 

[1]Department of Medicine, University of Padova, Via Giustiniani, 2, 35128, Padova, Italy

[2]Laboratory of Cytogenetics, University Hospital of Pisa, Pisa, Italy

[3]Laboratory of Molecular Genetics, University Hospital of Pisa, Pisa, Italy

[4]Unit of Bronchopneumology, Department of Pathophysiology and Transplantation, Fondazione IRCCS Ca’ Granda, Ospedale Maggiore Policlinico, University of Milan, Milan, Italy

[5]Unit of Pathological Anatomy, Department of Medical Biotechnology, University of Siena, Siena, Italy

关键词: Primary ciliary dyskinesia;    DNAI2;    Outer dynein arm;    PCD genetic panel;    Normal pressure hydrocephalus;   

DOI  :  10.1186/s12881-020-01160-5

来源: Springer

【 摘 要 】

BackgroundPrimary ciliary dyskinesia (PCD) is a highly heterogeneous genetic disorder caused by defects in motile cilia. The hallmark features of PCD are the chronic infections of the respiratory tract, moreover, clinical manifestations include also laterality defects and risk of male infertility.Clinical phenotypes of PCD are the result of mutations in genes encoding components of axonema or factors involved in axonemal assembly. Recent studies have identified over 45 PCD-associated genes, therefore, molecular analysis represents a powerful diagnostic tool to confirm and uncover new genetic causes of this rare disease.Case presentationHere, we describe a female infant of Moroccan origin with normal pressure hydrocephalus (NPH) in addition to most common PCD symptoms. Transmission Electron Microscopy (TEM) and molecular tests, such as a Next generation Sequencing panel and a custom array CGH, were performed for diagnosis of PCD. TEM revealed outer dynein arm (ODA) defects, whilst molecular analyses detected a novel 6,9 kb microdeletion in DNAI2 gene.ConclusionsSince DNAI2 mutations are very rare, this case report contributes to better delineate the important role of DNAI2 as causative of PCD phenotype, suggesting, furthermore, that the variations in DNAI2 may be as a new genetic risk factor for NPH. Indeed, although the association of hydrocephalus with PCD has been well documented, however, only a small number of human patients show this defect.Furthermore, this study highlights the importance of high-throughput technologies in advancing our understanding of heterogeneous genetic disorders.

【 授权许可】

CC BY