Founder mutation in RSPH4A identified in patients of hispanic descent with primary ciliary dyskinesia

M. Leigh Anne Daniels, Margaret W. Leigh, Stephanie Davis, Michael C. Armstrong, Johnny L. Carson, Milan Hazucha, Sharon D. Dell, Maria Eriksson, Francis S. Collins, Michael R. Knowles, Maimoona A. Zariwala

Research output: Contribution to journalArticle

19 Citations (Scopus)

Abstract

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_6delAAGT splice-site mutation in RSPH4A were Hispanic with ancestry tracing to Puerto Rico. This mutation is a founder mutation and a common cause of PCD without situs abnormalities in patients of Puerto Rican descent. Primary ciliary dyskinesia (PCD) is a rare, autosomal recessive, genetically heterogeneous disorder characterized by ciliary dysfunction resulting in chronic otosino-pulmonary disease, respiratory distress in term neonates, laterality (situs) defects, and bronchiectasis. Here, we describe a novel splice-site mutation (c.921+3_6delAAGT) in RSPH4A, which leads to a premature translation termination signal in nine Hispanic subjects with Puerto Rican ancestry with PCD. This mutation is a founder mutation and a common cause of PCD without situs abnormalities in patients of Puerto Rican descent.

Original languageEnglish
Pages (from-to)1352-1356
Number of pages5
JournalHuman Mutation
Volume34
Issue number10
DOIs
StatePublished - Oct 2013

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Kartagener Syndrome
Hispanic Americans
Mutation
Bronchiectasis
Lung Diseases
Newborn Infant
Puerto Rico
RNA Splice Sites
Genetic Testing
Electron Microscopy

Keywords

  • Cilia
  • Kartagener syndrome
  • RSPH4A
  • Sequencing

ASJC Scopus subject areas

  • Genetics
  • Genetics(clinical)

Cite this

Daniels, M. L. A., Leigh, M. W., Davis, S., Armstrong, M. C., Carson, J. L., Hazucha, M., ... Zariwala, M. A. (2013). Founder mutation in RSPH4A identified in patients of hispanic descent with primary ciliary dyskinesia. Human Mutation, 34(10), 1352-1356. https://doi.org/10.1002/humu.22371

Founder mutation in RSPH4A identified in patients of hispanic descent with primary ciliary dyskinesia. / Daniels, M. Leigh Anne; Leigh, Margaret W.; Davis, Stephanie; Armstrong, Michael C.; Carson, Johnny L.; Hazucha, Milan; Dell, Sharon D.; Eriksson, Maria; Collins, Francis S.; Knowles, Michael R.; Zariwala, Maimoona A.

In: Human Mutation, Vol. 34, No. 10, 10.2013, p. 1352-1356.

Research output: Contribution to journalArticle

Daniels, MLA, Leigh, MW, Davis, S, Armstrong, MC, Carson, JL, Hazucha, M, Dell, SD, Eriksson, M, Collins, FS, Knowles, MR & Zariwala, MA 2013, 'Founder mutation in RSPH4A identified in patients of hispanic descent with primary ciliary dyskinesia', Human Mutation, vol. 34, no. 10, pp. 1352-1356. https://doi.org/10.1002/humu.22371
Daniels, M. Leigh Anne ; Leigh, Margaret W. ; Davis, Stephanie ; Armstrong, Michael C. ; Carson, Johnny L. ; Hazucha, Milan ; Dell, Sharon D. ; Eriksson, Maria ; Collins, Francis S. ; Knowles, Michael R. ; Zariwala, Maimoona A. / Founder mutation in RSPH4A identified in patients of hispanic descent with primary ciliary dyskinesia. In: Human Mutation. 2013 ; Vol. 34, No. 10. pp. 1352-1356.
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