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Chronic Lung Disease in Cutis Laxa

Westman, Rachel E (2011) Chronic Lung Disease in Cutis Laxa. Master's Thesis, University of Pittsburgh. (Unpublished)

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BACKGROUND: Cutis laxa (CL) is a group of disorders characterized by loose, inelastic, and redundant skin. The different types of CL are distinguished by clinical features, inheritance, and molecular findings. The objective of this study was to characterize the pulmonary phenotype of the different types of CL based on age of onset (congenital, acquired/late-onset, or unknown) and mutational status. The first aim of this study was to collect clinical data to better define the pulmonary involvement in cutis laxa. The second aim was to determine if heterozygous carriers of recessive types of cutis laxa are susceptible to chronic lung disease. METHODS: Clinical questionnaires, medical histories, and pulmonary function tests (PFTs) were used to collect clinical data on patients with a confirmed or suspected diagnosis of CL and unaffected first-degree relatives with a known mutation (carriers). The clinical data was then compared between the groups categorized by age of onset and between those with known mutations (mutational status). RESULTS: The clinical questionnaires and medical histories of 83 CL patients with 8 acquired/late-onset, 52 congenital, and 23 of unknown etiology and 5 carriers were analyzed. In addition, mutations have been identified in 27 of the 83 patients in ELN, FBLN4, FBLN5, ATP6V0A2, or LTBP4, and the 5 carriers had mutations in either FBLN4 or LTBP4. The most common respiratory responses amongst the patients included pneumonia (24.1%), tachypnea (15.7%), and emphysema (12.0%). The only statistically significant finding was dyspnea in acquired/late-onset patients. Of those with a known mutation, 15 reported pulmonary involvement, with 10 of these individuals having at least one LTBP4 mutation. For the 13 PFTs collected, the 10 CL patients ranged from normal lung function to very severe obstruction, and 3 carriers were deemed to have normal function. An important new finding was the presence of pulmonary obstructive disease in those with ATP6V0A2 mutations. CONCLUSION: These results demonstrate a high prevalence and significant heterogeneity of pulmonary complications in CL. Further research is needed to determine any correlation between specific pulmonary findings and genotypes. PUBLIC HEALTH SIGNIFICANCE: Chronic lung disease is a common cause of morbidity in the general population. Uncovering the genetic basis of chronic lung disease in inherited syndromes has the potential to identify key molecular targets for improved diagnosis and treatment of common respiratory ailments.


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Item Type: University of Pittsburgh ETD
Status: Unpublished
CreatorsEmailPitt UsernameORCID
Westman, Rachel Erew49@pitt.eduREW49
ETD Committee:
TitleMemberEmail AddressPitt UsernameORCID
Committee ChairUrban, Zsolturbanz@pitt.eduURBANZ
Committee MemberWilson, Johnwilson@nsabp.pitt.eduJWW
Committee MemberMcConnell,
Committee MemberGrubs, Robinrgrubs@pitt.eduRGRUBS
Date: 29 June 2011
Date Type: Completion
Defense Date: 13 April 2011
Approval Date: 29 June 2011
Submission Date: 5 April 2011
Access Restriction: 5 year -- Restrict access to University of Pittsburgh for a period of 5 years.
Institution: University of Pittsburgh
Schools and Programs: School of Public Health > Genetic Counseling
Degree: MS - Master of Science
Thesis Type: Master's Thesis
Refereed: Yes
Uncontrolled Keywords: Chronic bronchitis; COPD; Elastin; Emphysema; Chronic obstructive pulmonary disease; Elastic fiber
Other ID:, etd-04052011-233306
Date Deposited: 10 Nov 2011 19:34
Last Modified: 15 Nov 2016 13:38


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