Interpretation of m.3243A>G in mtDNA in Clinical Expressivity Versus Tissue Heteroplasmy Ratios with Text Mining Analysis

Şahin G., Güleç Ç. , Başaran S. , Uyguner Z. O.

13th Balkan Congress of Human Genetics, Edirne, Türkiye, 17 - 20 Nisan 2019, ss.42

  • Yayın Türü: Bildiri / Özet Bildiri
  • Basıldığı Şehir: Edirne
  • Basıldığı Ülke: Türkiye
  • Sayfa Sayıları: ss.42


Introduction: MELAS (mitochondrial-encephalomyopathy, lactic-acidosis, and stroke-like episodes) is
multisystem disorder, typically presented between the ages of two to 40 years, associated with pathogenic
mtDNA variants. Approximately 80% of the patients present with m.3243A>G of MT-TL1 encoding
mitochondrial tRNA-leucine1 (UUA/G). Clinical variability basically attributed to the mutation load in tissues.
Material and method: 319 articles published on m.3243 A>G, between the years of 1995-2018, are investigated
for the number of cases attributed with age of definitive diagnosis, gender, inheritance, clinical and biochemical
spectrum and tissue distribution of the heteroplasmic ratios. Data recorded on spread-sheets, extracted to charts
by using Vim text editor, statistical analysis performed with Python. Results: 468 out of 730 total reported
atients’ data with heter lasmy revealed. 42,9% had my athies (201/468), 30.8% had ne r l gi al
symptoms (144/468), 16.7% had cardiovascular (78/468), 11% had ear/eye problems (53/468), and 4.1% had
gastrointestinal complications. Methods of heteroplasmy measurements differed in reports. Clinical groups
under additional findings of either with hearing loss, ocular abnormalities and endocrinological problems, 48
with 73.6±13.6%, 19 with 63.2±19.6% and 18 with 61.7±20.8% m tati n l ads were al lated. s le and
bl d meas rements in 79 atients were 63.6±19.3% and 25.7±19.3%, res e tively. Similarly, 17 atients’
rati s were re rted r rine and bl d, 55.9±21% and 20.7±10.4%, res e tively. Discussion: Leukocytes are
the major tissue used in diagnosis, nevertheless has lower accuracy. Urine was as valuable as muscle for
obtaining threshold values, moreover convenient since non-invasive. Majority of the m.3243A>G variant of
mtDNA was associated with myopathic findings and least with episodic vomiting.