Module 3: Lesson 8 – Monogenic Disorders


Name: Prof Michael Pepper
Affiliation: University of Pretoria & University of Geneva, Switzerland
Location: Pretoria, South Africa

Michael Pepper is Director of the Institute for Cellular and Molecular Medicine, Director of the SAMRC Extramural Unit for Stem Cell Research and Therapy, and a professor in the Department of Immunology in the Faculty of Health Sciences at the University of Pretoria (UP). He is also professeur associé in the Department of Genetic Medicine and Development in the Faculty of Medicine at the University of Geneva, Switzerland. Michael has worked extensively in the field of clinically-oriented (translational) molecular cell biology, and his current interests include stem cells and the human genome.

Name: Dr Cheryl Stewart
Affiliation: University of Pretoria
Location: Pretoria, South Africa
Cheryl Stewart is a researcher at the University of Pretoria with a background in molecular biology and bioinformatics. She has an interest in using these fields to address questions related to disease. Her previous work focused on identifying viruses of agricultural significance in her home country of Jamaica. Currently, she is using her skills to identify mutations in South African cystic fibrosis patients. The data she generates will assist with being able to accurately diagnose African CF patients. She enjoys the thrill of discovery and using science to make a difference.

Name: Ms Noelene Kinsley
Affiliation: Independent COnsultant
Location: Pretoria, South Africa
Noelene Kinsley is a genetic counsellor practicing in private. She completed her MSc Med Genetic Counselling at the University of the Witwatersrand and has been practicing in private since. She and her colleague established a company, GC Network (Pty) Ltd, to provide access to resources needed to help individuals make sense of how genetics affects their health and that of their families. Together, they ensure that people can access genetic counselling where appropriate. Noelene is currently the Chair for the Genetic Counsellors of South Africa, a focus group of the Southern African Society of Human Genetics. Her personal interests include genetic counselling for monogenic disorders, with special interest in cancer genetics, ophthalmic genetics, preconception and prenatal genetic counselling, and Huntington disease. Noelene’s overall passion is that anyone who needs to understand how genetics impacts their lives can access appropriate professional support regardless of their socio-economic standing.

The course will provide information on the inheritance patterns of monogenic diseases. In order to facilitate understanding, we will describe the inheritance patterns of cystic fibrosis (CF) which is one of the most common autosomal recessive monogenic disorders. Information will be provided on basic counselling techniques including an understanding of the probability of a carrier couple having a CF-affected child. An outline of treatment options for CF patients will also be provided.

Learning Outcomes

  • Identify individuals that would benefit from the knowledge of a monogenic disorder and the impact on their health and that of their family. Including;
    Families with a diagnosis of a monogenic disorder
    Child with a diagnosis of a monogenic disorder
    High risk for a monogenic disorder based on population risks
    Preconception/premarital testing.
  • Ability to inform individuals on monogenic disorders to enable them to understand and make personal decisions regarding the options available to them in the context of their community, including their beliefs and culture.
  • List available options for diagnosis, treatment, support and care, including the limitations.
  • Discuss ethical, legal and social implication of the diagnosis of a monogenic disorder.

Class Videos

Class Slides

Class Assessments: Pre-Class Exercise
Choose one monogenic disorder prevalent in your area (examples include Duchenne muscular dystrophy, neurofibromatosis, sickle cell anaemia, familial hypercholesterolemia etc). For information you can refer to the website suggested in Week 04

1. List the symptoms associated with the disorder
2. What kind of information about the disorder you have chosen would you give a patient in their initial genetic counselling session ( should include the mode of inheritance, risks to family members and at least one diagnostic test which can be done for the disorder).

Assessment:  Class exercise
Module3_Lecture8_ClassExerciseGenomics of Monogenic Disorders
Module3_Lecture8_ClassExerciseGenomics of Monogenic Disorders

Question 1: Based on the discussions and summary of cystic fibrosis (CF) consider how to help the following family:
A couple arrives at the clinic. The man (John) is of European descent and the woman (Berth) is of Xhosa descent (South Africa tribe). Berth is 12 weeks pregnant. They want to know the risk of CF for their child. John has two brothers, one of whom has a son and a daughter. The daughter was diagnosed with CF and her brother has a son with CF. John has a sister with CF. John’s sister is 23 years old and needs a lung transplant. Berth has a healthy sister. Berth’s brother died as a child after repeated chest infections. Berth knows that her family does not carry CF as it is only diagnosed in people from Europe. Berth also knows she is not a carrier as she had a carrier screening test.
Draw a pedigree. Include obligate carriers.

What is the pattern of inheritance for John’s brother and his children?
What do you think would cause this?
Do you think the John’s sister is affected because their parents are cousins?
How would you determine the risk of CF for John and Berth’s child?
Is Berth definitely not a carrier?
Question 2: There are two children with CF. The first child has F508del/3120+1G>A, and the second has R334W/G551D. Search for these combinations of CF mutations at What does the CFTR2 website say about the severity of the phenotype these children can expect to experience? Is either child a candidate for mutation-specific treatment?

Class Evaluation
See course evaluations section.

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