The given sentence is missing in the paragraph below. Decide where it best fits among the options 1, 2, 3, or 4 indicated in the paragraph.
Sentence: In each of the affected individuals, the metabolic abnormality was traced to a single enzyme in the mitochondrial matrix.
Paragraph: The earliest documented link between a hereditary metabolic disorder and severe neurological decline came from a clinical survey in 1987. ___(1)___ Biochemical and enzymatic assays were performed on a large Finnish family in which several siblings presented with a syndrome of developmental regression and episodic lethargy. ___(2)___ The clinical deterioration included seizures, loss of motor milestones, and recurrent coma. ___(3)___ A missense mutation was identified in the coding region of the pyruvate dehydrogenase complex E1-alpha gene which substitutes an arginine for a histidine. ___(4)___
Sentence: In each of the affected individuals, the metabolic abnormality was traced to a single enzyme in the mitochondrial matrix.
Paragraph: The earliest documented link between a hereditary metabolic disorder and severe neurological decline came from a clinical survey in 1987. ___(1)___ Biochemical and enzymatic assays were performed on a large Finnish family in which several siblings presented with a syndrome of developmental regression and episodic lethargy. ___(2)___ The clinical deterioration included seizures, loss of motor milestones, and recurrent coma. ___(3)___ A missense mutation was identified in the coding region of the pyruvate dehydrogenase complex E1-alpha gene which substitutes an arginine for a histidine. ___(4)___
Answer and solution
Correct answer: A
Solution
The paragraph moves from the study, to the methods (assays on a Finnish family), to the symptoms (seizures, lost milestones, coma). The enzyme localisation should come next, before the precise point mutation. At (1) it would come before the study is introduced; at (2) it breaks the link between the family and the assays; at (4) it would follow the more specific mutation detail. So blank (3).