{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,6]],"date-time":"2026-10-06T08:23:12Z","timestamp":1791274992295,"version":"4.1.0"},"reference-count":36,"publisher":"BMJ","issue":"6","content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["J Med Genet"],"accepted":{"date-parts":[[2012,4,18]]},"published-print":{"date-parts":[[2012,6]]},"abstract":"<jats:sec>\n                    <jats:title>Background<\/jats:title>\n                    <jats:p>\n                      <jats:italic>CCDC39<\/jats:italic>\n                      and\n                      <jats:italic>CCDC40<\/jats:italic>\n                      genes have recently been implicated in primary ciliary dyskinesia (PCD) with inner dynein arm (IDA) defects and axonemal disorganisation; their contribution to the disease is, however, unknown. Aiming to delineate the\n                      <jats:italic>CCDC39\/CCDC40<\/jats:italic>\n                      mutation spectrum and associated phenotypes, this study screened a large cohort of patients with IDA defects, in whom clinical and ciliary phenotypes were accurately described.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>\n                      All\n                      <jats:italic>CCDC39<\/jats:italic>\n                      and\n                      <jats:italic>CCDC40<\/jats:italic>\n                      exons and intronic boundaries were sequenced in 43 patients from 40 unrelated families. The study recorded and compared clinical features (sex, origin, consanguinity, laterality defects, ages at first symptoms and at phenotype evaluation, neonatal respiratory distress, airway infections, nasal polyposis, otitis media, bronchiectasis, infertility), ciliary beat frequency, and quantitative ultrastructural analyses of cilia and sperm flagella.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>\n                      Biallelic\n                      <jats:italic>CCDC39<\/jats:italic>\n                      or\n                      <jats:italic>CCDC40<\/jats:italic>\n                      mutations were identified in 30\/34 (88.2%) unrelated families with IDA defects associated with axonemal disorganisation (22 and eight families, respectively). Fourteen of the 28 identified mutations are novel. No mutation was found in the six families with isolated IDA defects. Patients with identified mutations shared a similar phenotype, in terms of both clinical features and ciliary structure and function. The sperm flagellar ultrastructure, analysed in 4\/7 infertile males, showed evidence of abnormalities similar to the ciliary ones.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusions<\/jats:title>\n                    <jats:p>\n                      <jats:italic>CCDC39<\/jats:italic>\n                      and\n                      <jats:italic>CCDC40<\/jats:italic>\n                      mutations represent the major cause of PCD with IDA defects and axonemal disorganisation. Patients carrying\n                      <jats:italic>CCDC39<\/jats:italic>\n                      or\n                      <jats:italic>CCDC40<\/jats:italic>\n                      mutations are phenotypically indistinguishable.\n                      <jats:italic>CCDC39<\/jats:italic>\n                      and\n                      <jats:italic>CCDC40<\/jats:italic>\n                      analyses in selected patients ensure mutations are found with high probability, even if clinical or ciliary phenotypes cannot prioritise one analysis over the other.\n                    <\/jats:p>\n                  <\/jats:sec>","DOI":"10.1136\/jmedgenet-2012-100867","type":"journal-article","created":{"date-parts":[[2012,6,12]],"date-time":"2012-06-12T10:08:00Z","timestamp":1339495680000},"page":"410-416","source":"Crossref","is-referenced-by-count":93,"title":["Delineation of\n                    <i>CCDC39\/CCDC40<\/i>\n                    mutation spectrum and associated phenotypes in 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