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High-speed Video Microscopy Analysis for First-line Diagnosis of Primary Ciliary Dyskinesia
Published on: January 19, 2022
Primary ciliary dyskinesia-causing mutations in Amish and Mennonite communities
Thomas W Ferkol1, Erik G Puffenberger, Hauw Lie
1Department of Pediatrics, Washington University in St Louis, St Louis, MO 63110, USA. ferkol_t@kids.wustl.edu
The Journal of Pediatrics
|March 13, 2013
Summary
Primary ciliary dyskinesia (PCD) in Amish and Mennonite populations is often caused by a shared founder mutation in the DNAH5 gene. However, genetic heterogeneity exists, with other PCD-associated gene mutations also identified.
Area of Science:
- Genetics
- Rare diseases
- Population genetics
Background:
- Primary ciliary dyskinesia (PCD) is a rare genetic disorder affecting cilia function.
- Amish and Mennonite communities are socially isolated populations with unique genetic profiles.
- Founder mutations can explain the prevalence of certain genetic diseases in these communities.
Purpose of the Study:
- To investigate if a single founder mutation causes primary ciliary dyskinesia (PCD) in unrelated Amish and Mennonite families.
- To identify the specific genetic mutation responsible for PCD in these populations.
Main Methods:
- Clinical characterization and measurement of nasal nitric oxide levels in affected individuals and relatives.
- Ciliary ultrastructural analyses and DNA isolation.
- Genome-wide homozygosity mapping, linkage analyses, targeted mutation analyses, and exome sequencing.
Main Results:
- A recurrent nonsense DNAH5 mutation (c.4348C>T, p.Q1450X) was identified in Amish and Mennonite subjects from geographically dispersed communities.
- This DNAH5 mutation was found to be a founder mutation, common to these populations due to shared heritage.
- Other DNAH5 mutations and mutations in different PCD-associated genes were also found, indicating genetic heterogeneity.
Conclusions:
- The same founder DNAH5 mutation is a significant cause of primary ciliary dyskinesia (PCD) in Amish and Mennonite populations.
- Despite the common founder mutation, genetic heterogeneity in PCD exists within these consanguineous communities.
- Further research into the genetic basis of PCD in isolated populations is warranted.
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