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Founder Mutation in RSPH4A Identified in Patients of Hispanic Descent with Primary Ciliary Dyskinesia
Author(s) -
Daniels M. Leigh Anne,
Leigh Margaret W.,
Davis Stephanie D.,
Armstrong Michael C.,
Carson Johnny L.,
Hazucha Milan,
Dell Sharon D.,
Eriksson Maria,
Collins Francis S.,
Knowles Michael R.,
Zariwala Maimoona A.
Publication year - 2013
Publication title -
human mutation
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.981
H-Index - 162
eISSN - 1098-1004
pISSN - 1059-7794
DOI - 10.1002/humu.22371
Subject(s) - primary ciliary dyskinesia , biology , cilium , situs inversus , bronchiectasis , mutation , genetics , splice site mutation , pathology , anatomy , medicine , rna splicing , lung , gene , rna
Primary ciliary dyskinesia ( PCD ) is a rare, autosomal recessive, genetically heterogeneous disorder characterized by ciliary dysfunction resulting in chronic oto‐sino‐pulmonary disease, respiratory distress in term neonates, laterality (situs) defects, and bronchiectasis. Diagnosis has traditionally relied on ciliary ultrastructural abnormalities seen by electron microscopy. Mutations in radial spoke head proteins occur in PCD patients with central apparatus defects. Advances in genetic testing have been crucial in addressing the diagnostic challenge. Here, we describe a novel splice‐site mutation (c.921+3_6delAAGT) in RSPH4A , which leads to a premature translation termination signal in nine subjects with PCD (seven families). Loss‐of‐function was confirmed with quantitative ciliary ultrastructural analysis, measurement of ciliary beat frequency and waveform, and transcript analysis. All nine individuals carrying c.921+3_6del AAGT splice‐site mutation in RSPH4A were H ispanic with ancestry tracing to P uerto R ico. This mutation is a founder mutation and a common cause of PCD without situs abnormalities in patients of P uerto R ican descent.