WBR0385
| Author | [[PageAuthor::Rim Halaby, M.D. [1]]] |
|---|---|
| Exam Type | ExamType::USMLE Step 1 |
| Main Category | MainCategory::Genetics |
| Sub Category | SubCategory::Renal |
| Prompt | [[Prompt::A 12 year old male patient is brought by his mother to the physician’s office for red-colored urine. Upon further questioning, the mother explains that the patient also has deafness and eye problems. The physician suspects a collagen disease. Genetic studies reveal a mutation of COL4A5 and confirm the diagnosis with mutation encoding α chains. What is the mode of inheritance of the patient’s condition?]] |
| Answer A | AnswerA::X-linked dominant |
| Answer A Explanation | AnswerAExp::Alport Syndrome (AS) is transmitted in an X-linked pattern when mutation of COL4A5 that encodes α5 chain occurs |
| Answer B | AnswerB::Autosomal recessive |
| Answer B Explanation | AnswerBExp::Mutations of COL4A3 and COL4A4 that cause AS are transmitted by autosomal recessive pattern. |
| Answer C | AnswerC::Autosomal dominant |
| Answer C Explanation | AnswerCExp::AS is rarely transmitted in autosomal dominant pattern. Common examples of autosomal dominant transmission include neurofibromatosis I and II, tuberous sclerosis, and Huntington disease. |
| Answer D | AnswerD::Mitochondrial |
| Answer D Explanation | AnswerDExp::AS is not transmitted in mitochondrial pattern. Examples of mitochondrial diseases include MELAS and MERRF. |
| Answer E | AnswerE::Polygenic |
| Answer E Explanation | AnswerEExp::AS is not considered polygenic. Common polygenic diseases include diabetes, schizophrenia, and alopecia. |
| Right Answer | RightAnswer::A |
| Explanation | [[Explanation::Alport Syndrome (AS) is an inherited disorder of type IV collagen with abnormal glomerular basement membrane, hematuric nephropathy, and sensorineural deafness. AS is genetically heterogeneous. It is associated with several genetic mutations; most commonly: COL4A3, COL4A4, and COL4A5.
COL4A3 and COL4A4 encoding α3 and α4 respectively are 2 genes located on chromosome 2. AS due to these 2 genes would be of an autosomal recessive inheritance. In contrast, COL4A5 encoding α5 is a gene on chromosome X. AS due to COL4A5 mutation would be of an X-linked inheritance. X-linked transmission could be either dominant or recessive. Educational Objective: Alport Syndrome (AS) can be transmitted either in an X-linked pattern when mutation of COL4A5 that encodes α5 chain occurs, or in an autosomal recessive pattern when mutation of COL4A3 and COL4A4 that encode α3 and α4 respectively. Reference:
Haas M. Alport syndrome and thin glomerular basement membrane nephropathy. A practical approach to diagnosis. Archives of Pathology and Laboratory Medicine. 2009;133(2):224-232 |
| Approved | Approved::No |
| Keyword | |
| Linked Question | Linked:: |
| Order in Linked Questions | LinkedOrder:: |