1st March 2024

Common Single-Gene Disorders

Examples

Autosomal dominant

Approximately 1500 conditions have been identified to be inherited in an autosomal dominant fashion. As a rule of thumb, these conditions can be seen to be caused by “structural disorders”. Examples include:

*This is inherited in a codominant pattern whereby different mutations affecting the same gene can be expressed within a phenotype.

Autosomal recessive

Approximately 1000 different conditions have been identified to be inherited by an autosomal recessive pattern, and this often presents as a “metabolic disorder”. Examples include:

*Alpha thalassaemia’s inheritance is complex due to 2 genes contributing towards the formation of the α-globin chain.

**This only applies to certain types – Various types of spinocerebellar ataxia are inherited in an autosomal dominant pattern.

X-linked dominant

X-linked dominant conditions are rare and affect males and females equally. X-inactivation often means that females will have a milder phenotype compared to males. Examples include:

X-linked recessive

X-linked recessive conditions usually affect males, with females acting as carriers unless the female has a homozygous genotype. Females may have mild phenotypes due to skewed X-inactivation. Examples include:

Non-mendelian

We will provide a few common genetic conditions that may come up during the MRCP examination that does not display the typical Mendelian inheritance, including chromosomal abnormalities. Examples include:

References

• Firth, H. V., & Hurst, J. A. (2017). Oxford Desk Reference: Clinical Genetics and Genomics: Oxford University Press.
• Bessant, R., Birns, J., & Ford, C. (2020). Medicine for MRCP.
• Ralston, S. H., Penman, I. D., Strachan, M. W., & Hobson, R. (2018). Davidson’s Principles and Practice of Medicine E-Book: Elsevier Health Sciences.
• Kingston, H. M. (2002). ABC of clinical genetics: London: Blackwell Publishing Ltd.