WBR0385
| Author | [[PageAuthor::Yazan Daaboul, M.D. (Reviewed by Yazan Daaboul, M.D. and Alison Leibowitz [1])]] |
|---|---|
| Exam Type | ExamType::USMLE Step 1 |
| Main Category | MainCategory::Genetics |
| Sub Category | SubCategory::Renal |
| Prompt | [[Prompt::A 12-year-old boy is brought by his mother to the physician’s office for red-colored urine. Upon further questioning, the mother explains that her son is deaf and has eye problems. The physician suspects a collagen disease. Genetic studies reveal a mutation of COL4A5 the encodes collagen α chains. What is the most likely mode of inheritance of this patient’s condition?]] |
| Answer A | AnswerA::X-linked dominant |
| Answer A Explanation | AnswerAExp::Alport Syndrome (AS) can be inherited in an X-linked pattern due to a mutation in ''COL4A5''. |
| Answer B | AnswerB::Autosomal recessive |
| Answer B Explanation | AnswerBExp::Mutations in ''COL4A3'' and ''COL4A4'' that result in AS are usually inherited in an autosomal recessive pattern. |
| Answer C | AnswerC::Autosomal dominant |
| Answer C Explanation | AnswerCExp::Alport syndrome is rarely inherited in an autosomal dominant pattern. |
| Answer D | AnswerD::Mitochondrial |
| Answer D Explanation | AnswerDExp::Alport syndrome is not a mitochondrial disease. Examples of mitochondrial diseases are MELAS and MERRF. |
| Answer E | AnswerE::Polygenic |
| Answer E Explanation | [[AnswerEExp::Alport syndrome is not considered a polygenic disease. Common polygenic diseases include schizophrenia and heart disease. Polygenic disease refers to a disease in which multiple genetic loci are thought to contribute to disease risk in the same individual (many risk/protective alleles of low affect size). This concept is distinct from the idea of locus heterogeneity, where mutations in separate genes can cause the same Mendelian syndrome. Alport syndrome and hypertrophic cardiomyopathy are examples of Mendelian diseases with locus heterogeneity.]] |
| Right Answer | RightAnswer::A |
| Explanation | [[Explanation::Alport Syndrome (AS) is an inherited disorder of type IV collagen with thinning and splitting of glomerular basement membranes, hematuric nephropathy, and sensorineural deafness. Alport Syndrome may be caused by mutations in several genes of the collagen family (locus heterogeneity), including COL4A3, COL4A4, and COL4A5. More than 80% of cases of Alport syndrome are caused by mutations in COL4A5, a gene that encodes the α5 subunit of basement membrane-associated collagen type IV. COL4A5 is located on the X chromosome, and Alport syndrome related to this locus therefore follows an X-linked dominant mode of inheritance. COL4A3 and COL4A4, which encode α3 and α4 respectively, are located on chromosome 2. Alport syndrome that results from mutations in COL4A3 and COL4A4 usually follows an autosomal recessive pattern of inheritance. Autosomal dominant pattern of inheritance is rare. Educational Objective: Alport Syndrome (AS) is usually inherited in an X-linked dominant pattern due to a mutation in COL4A5. Less commonly, it is inherited in an autosomal recessive pattern due to a mutation in COL4A3 or COL4A4. |
| Approved | Approved::Yes |
| Keyword | WBRKeyword::Genetics, WBRKeyword::Deafness, WBRKeyword::Blind, WBRKeyword::Hematuria, WBRKeyword::X-linked, WBRKeyword::X-linked dominant, WBRKeyword::COL4A5, WBRKeyword::Basement membrane, WBRKeyword::Alport syndrome |
| Linked Question | Linked:: |
| Order in Linked Questions | LinkedOrder:: |