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Question 581
Genetics → General
Classification
Question
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Which interpretation best supports investigating one mitochondrial genetic defect as a possible explanation for all three findings?
Question Stem
A patient has neurological abnormalities, myopathy and cardiomyopathy. A candidate sequence variant has been found in mitochondrial DNA, and investigation also indicates abnormal cytochrome oxidase function. The investigator notes that the mitochondrial genome contains only 37 genes and questions whether such a small genome could plausibly account for disease in several different tissues.
Options
A
Mitochondrial genes are essential for mitochondrial function and are expressed in neuronal and other mitochondria-rich tissues
B
Mitochondrial DNA cannot encode enzyme information, so the sequence variant must instead be nuclear
C
Mitochondrial genes are expressed only in neuronal tissue, so the variant can explain neurological findings alone
D
A mitochondrial gene can affect only one tissue type, so three separate genetic defects are required
E
A genome containing only 37 genes is too small for its mutations to cause clinically important dysfunction
Explanation
The mitochondrial genome's small size does not imply an unimportant role. Its 37 genes are essential for normal mitochondrial function, and mitochondrial DNA includes information for certain cytochrome oxidase enzymes. Expression in neuronal tissue and other tissues rich in mitochondria provides a coherent basis for neurological abnormalities, myopathy and cardiomyopathy occurring together. These findings justify investigating a shared mitochondrial mechanism; they do not by themselves prove that the particular sequence variant is causal.
Option Validity
B) Mitochondrial DNA has its own genome and can encode information for enzymes, including certain cytochrome oxidase enzymes.
C) Expression is not confined to neuronal tissue; other mitochondria-rich tissues are also involved.
D) The distribution of mitochondrial gene expression permits one mitochondrial mechanism to affect more than one tissue type.
E) The 37 mitochondrial genes are essential for normal function, and their abnormalities can be associated with neurological, muscle and cardiac disease.
Further Reading
Saxena R. Textbook for MRCOG-1: Basic Sciences in Obstetrics and Gynaecology. Jaypee Brothers Medical Publishers; 2016. Chapter 8, Genetics: Mitochondrial DNA. Printed pages 255–256.