WBR0436

Author	[[PageAuthor::Rim Halaby, M.D. [1]]]
Exam Type	ExamType::USMLE Step 1
Main Category	MainCategory::Genetics
Sub Category	SubCategory::Reproductive
Prompt	[[Prompt::A 2-month-old male is brought by his parents to the pediatrician’s office for multiple fractures with minimal trauma. Upon genetic testing, you find that the patient has osteogenesis imperfecta, which is most commonly inherited in an autosomal dominant pattern. Familial genetic analysis reveals that the patient’s mother has a mutant genotype of osteogenesis imperfecta, but she is not affected by the disease. Which genetic characteristic best explains this finding?]]
Answer A	AnswerA::Variable expression
Answer A Explanation	AnswerAExp::Variable expression is the range of disease symptoms and severity from one person to another who in fact have the same mutation. Neurofibromatosis type I is a classical example of variable expression.
Answer B	AnswerB::Incomplete penetrance
Answer B Explanation	AnswerBExp::Incomplete penetrance is when not all people with the mutant genotype express the phenotype, such as OI.
Answer C	AnswerC::Locus heterogeneity
Answer C Explanation	[[AnswerCExp::Locus heterogeneity is defined as several mutations in several genes may eventually have the same phenotype. A classical example if Marfanoid habitus that is expressed with mutations of FBN1 gene that causes Marfan syndrome, and with genetic mutations that cause MEN2B syndrome and homocystinuria.]]
Answer D	AnswerD::Heteroplasmy
Answer D Explanation	AnswerDExp::Heteroplasmy is the presence of more than one mitochondrial DNA type that results in variable expression of mitochondrial inherited disease.
Answer E	AnswerE::Imprinting
Answer E Explanation	[[AnswerEExp::Imprinting is the situation when the phenotype of the patient depends on whether it is derived from the father or the mother. 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 a specific example of incomplete penetrance. The majority of OI cases has a dominant mutation in one of the two genes that produce type I collagen: COL1A1 or COL1A2. Incomplete penetrance is defined as the unpredictable presence of mutant phenotype in individuals despite the confirmed presence of the mutant genotype. As such, not all patients who have the mutation will express it. In this example, the child has the mutant genotype and expressed OI, whereas his mother also has the disease but did not express it and is thus not affected with OI. Educational Objective: Incomplete penetrance is defined as the unpredictable presence of mutant phenotype in individuals despite the confirmed presence of the mutant genotype. As such, not all patients who have the mutation will express it. Educational Objective: References: ]]
Approved	Approved::No
Keyword	WBRKeyword::incomplete, WBRKeyword::penetrance, WBRKeyword::osteogenesis, WBRKeyword::imperfecta, WBRKeyword::autosomal, WBRKeyword::dominant, WBRKeyword::mutation
Linked Question	Linked::
Order in Linked Questions	LinkedOrder::