WBR0436

Author	[[PageAuthor::Yazan Daaboul, M.D. (Reviewed by Alison Leibowitz) (Reviewed by Serge Korjian)]]
Exam Type	ExamType::USMLE Step 1
Main Category	MainCategory::Genetics
Sub Category	SubCategory::Reproductive
Prompt	[[Prompt::A 2-month-old boy is brought the pediatrician’s office for a history of multiple fractures with minor trauma. Work-up reveals the patient has osteogenesis imperfecta. The pediatrician explains to the family that the disease is most commonly inherited in an autosomal dominant pattern. Genetic analysis of both parents reveals that the child’s mother has a genotype similar to that of her son, but is not affected by the disease. Which of the following genetic characteristics best explains this finding?]]
Answer A	AnswerA::Variable expression
Answer A Explanation	[[AnswerAExp::Variable expression is the range of disease symptoms and severity in individuals who have the same mutation. Neurofibromatosis type I is an example of variable expression.]]
Answer B	AnswerB::Incomplete penetrance
Answer B Explanation	[[AnswerBExp::Incomplete penetrance is when not all individuals with a mutant genotype express the phenotype, such as OI.]]
Answer C	AnswerC::Locus heterogeneity
Answer C Explanation	AnswerCExp::Locus heterogeneity is defined as mutations at different locations that result in the same phenotype.
Answer D	AnswerD::Heteroplasmy
Answer D Explanation	AnswerDExp::Heteroplasmy is the presence of more than one mitochondrial DNA type, resulting in variable expression of a mitochondrial inherited disease.
Answer E	AnswerE::Imprinting
Answer E Explanation	[[AnswerEExp::Imprinting is the situation when a phenotype is dependent on whether a particular gene is or is not methylated. For example, Prader-Willi and Angelman’s syndromes are both mutations of the same region in chromosome 15; but the disease is caused by a mutation derived paternally in Prader-Willi, whereas it is derived maternally in Angelman’s syndrome.]]
Right Answer	RightAnswer::B
Explanation	[[Explanation::Osteogenesis imperfecta (OI) is an example of incomplete penetrance. The majority of OI cases have a dominant mutation in one of the two genes that produce type I collagen: COL1A1 or COL1A2. Incomplete penetrance is the presence of an ordinary phenotype in an individual despite the confirmed presence of a mutant genotype. In this scenario, the child has a mutant genotype and expressed OI, whereas his mother also has the mutation in her genotype but did not express it phenotypically. Educational Objective: Incomplete penetrance is defined as is the presence of an ordinary phenotype in an individual despite the confirmed presence of a mutant genotype. References: First Aid 2014 page 84]]
Approved	Approved::Yes
Keyword	WBRKeyword::Incomplete penetrance, WBRKeyword::Osteogenesis imperfecta, WBRKeyword::Autosomal dominant, WBRKeyword::genetics, WBRKeyword::Inheritance
Linked Question	Linked::
Order in Linked Questions	LinkedOrder::