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Harvey Cushing Treated the First Known Patient With Carney Complex
Cynthia J Tsay1, Constantine A Stratakis2, Fabio Rueda Faucz2
1Yale University School of Medicine, New Haven, Connecticut 06510.
Journal of the Endocrine Society
|December 22, 2017
Summary
Carney complex (CNC), a genetic disorder, was molecularly confirmed in a patient from 1914 using archived tissue. This study highlights the value of historical records and modern genetic analysis in diagnosing rare endocrine diseases.
Area of Science:
- Endocrinology
- Genetics
- Molecular Biology
Background:
- Carney complex (CNC) is an endocrine disorder characterized by hyperplasia of endocrine organs, potentially causing Cushing syndrome and acromegaly due to adrenal and pituitary tumors.
- Mutations in the protein kinase A type I-alpha (PRKAR1A) gene have been associated with Carney complex.
Purpose of the Study:
- To investigate the genetic basis of Carney complex (CNC) in historical patient samples.
- To explore the conservation of genetic mutations linked to acromegaly, CNC, and Cushing syndrome over time.
Main Methods:
- DNA was extracted from archived hypothalamic, thalamic, or pituitary adenoma tissues from patients operated on by neurosurgeon Harvey Cushing (1913-1932).
- Genetic sequencing was performed on genes including PRKAR1A, AIP, USP8, GNAS1, and GPR101.
Main Results:
- A patient described by Dr. Cushing in 1914, with findings suggestive of CNC, was genetically analyzed.
- Sequencing revealed a germline heterozygous p.Arg74His mutation in the PRKAR1A gene within the patient's hypothalamus and pituitary adenoma, representing a novel amino acid change at a known mutation site.
Conclusions:
- This represents the first molecularly confirmed case of Carney complex (CNC).
- The study demonstrates the efficacy of modern genetic techniques in analyzing historical tissues.
- Detailed clinical documentation is crucial for diagnosing complex endocrine syndromes.