Q&A: Concerning Inherited Ion Channel Diseases

Genetic testing can allow tailored interventions to prevent or treat disease or disease complications. Appropriate use of genetic testing, including understanding the limitations and challenges of available testing approaches, is crucial to the successful use of genetic testing in improving health and quality of life.

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This is a Question & Answer revision article designed for medical students and professionals preparing for the PLAB, MRCP or USMLE examinations. They are based on actual questions from these examinations. You may find more useful one of our many articles on Diseases & Conditions, Medical Syndromes, Health & Wellness or Home Remedies.

In this article:
Terminology and genomic disorders
MCQ: clinical scenario
MCQ: answer
MCQ: explanation

Terminology and genomic disorders

The genotype can be defined as the DNA blueprint that is associated with the clinical manifestations of a trait or disease (the phenotype). Genetic testing can refer to any type of testing that helps determine an individual's genotype. It can be determined for the germline (cells arising from the germ cells and applicable to the vast majority of cells in the body) or for selected somatic cells such as tumor cells.

The term "genotyping" is used differently in two different contexts:

• Determining the genotype.
• Referring to a certain type of microarray that determines the genotype for a subset of selected nucleotide variants.

Genomic disorders are diseases that result from the loss or gain of chromosomal/DNA material (copy number variations [CNVs]). There are a number of well-delineated genomic disorders that can be divided in two categories: those resulting from copy number losses (deletion syndromes) and copy number gains (duplication syndromes).

MCQ: clinical scenario

A growing number of human diseases have been discovered to be caused by inherited mutations in genes encoding channels.

What inherited ion-channel diseases affects the chloride channel?

a) Liddle's syndrome
b) Cystic fibrosis
c) Hemoglobin M disease
d) Becker's muscular dystrophy
e) X-linked hereditary nephritis

MCQ: answer

The correct answer is B

MCQ: explanation

The gene responsible for Cystic fibrosis encodes a membrane-associated protein called the cystic fibrosis transmembrane regulator. The most common gene mutation, F508, leads to absence of a phenylalanine residue at position 508 on the CFTR protein which is a part of a cAMP-regulated Cl channel and appears to regulate Cl and Na transport across epithelial membranes. Heterozygotes may show subtle abnormalities of epithelial transport but are clinically normal.

Reference(s)
1). UpToDate: Genetic testing. Available online: https://www.uptodate.com/contents/genetic-testing
2). UpToDate: Genomic disorders: An overview. Available online: https://www.uptodate.com/contents/genomic-disorders-an-overview