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Investigation of the common MELAS mutation in the Northwestern Pennsylvania Amish community: mutation frequency and effectiveness of an educational intervention

Irani, Afifa (2015) Investigation of the common MELAS mutation in the Northwestern Pennsylvania Amish community: mutation frequency and effectiveness of an educational intervention. Master's Thesis, University of Pittsburgh. (Unpublished)

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Although mitochondrial respiratory chain deficiencies (often called “mitochondrial disease”) affect an estimated 1 in 5,000 individuals world-wide, prior to the recent diagnosis of this study’s index patient, mitochondrial DNA (mtDNA) mutations were not previously reported in Amish communities. The index patient from the Northwestern Pennsylvania Amish community was diagnosed with MELAS (Mitochondrial Encephalomyopathy, Lactic Acidosis, Stroke-like Episodes), the most common maternally-inherited mitochondrial disorder, and carries the common MELAS mutation, m.3243A>G in the MT-TL1 gene. Subsequently, two additional Amish families with different mitochondrial mutations were identified. These findings prompted a study with three aims: characterizing the incidence and clinical features of this MELAS mutation in this community, constructing a detailed pedigree of the Amish community, and assessing by pre- and post-intervention questionnaires the efficacy of an educational intervention designed to increase understanding of MELAS and mitochondrial disease.
A study visit to the community was attended by the index patient’s extended family. During this visit, an educational intervention was presented, and questionnaires were administered. Interviews were conducted to gather family history information, including family structure and the presence of mitochondrial disease symptoms in family members. Samples were collected from 13 adults and two children for genetic testing. Samples were analyzed using high-resolution melt profiling for targeted assessment of the m.3243A>G mutation. While data analysis of questionnaires demonstrated limited increased understanding of educational intervention material, anecdotal experiences support increased understanding. Genetic testing revealed the mutation of interest in 13 participants, with tissue-specific variations in the levels of heteroplasmy. At a follow-up visit, test results and their implications were disclosed and discussed through genetic counseling.
This study’s findings suggest maternally-inherited mitochondrial disease may be under-recognized given the lack of previous diagnosis in 13 participants reported here. The public health significance demonstrated through this is the potential for similarly unrecognized mitochondrial disease in the larger Amish community and in the general population due to the challenges related to diagnosis. Results of efficacy analysis of an educational intervention in this community can also inform the development of educational interventions for the general population and for health care providers about mitochondrial and other rare genetic disease.


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Item Type: University of Pittsburgh ETD
Status: Unpublished
CreatorsEmailPitt UsernameORCID
Irani, Afifaaei5@pitt.eduAEI5
ETD Committee:
TitleMemberEmail AddressPitt UsernameORCID
Thesis AdvisorWalsh Vockley,
Committee MemberKammerer, Candace Mcmk3@pitt.eduCMK3
Committee MemberShaffer, John, john.r.shaffer@gmail.comJRS51
Committee MemberVockley, Gerardgerard.vockley@chp.eduGEV1
Date: 9 June 2015
Date Type: Publication
Defense Date: 14 April 2015
Approval Date: 9 June 2015
Submission Date: 6 April 2015
Access Restriction: No restriction; Release the ETD for access worldwide immediately.
Number of Pages: 195
Institution: University of Pittsburgh
Schools and Programs: School of Public Health > Human Genetics
Degree: MS - Master of Science
Thesis Type: Master's Thesis
Refereed: Yes
Uncontrolled Keywords: MELAS, mitochondrial disease, Mitochondrial Encephalomyopathy Lactic Acidosis and Stroke-like Episodes, maternal inheritance, mitochondrial inheritance, genetics, human genetics, Mercer County, Northwestern Pennsylvania Amish, Mercer County Amish, Mercer PA, Mitochondrial Encephalomyopathy Lactic Acidosis Stroke-like Episodes, mitochondrial genetics
Date Deposited: 09 Jun 2015 13:51
Last Modified: 19 Dec 2016 14:42


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