Grange syndrome due to homozygous YY1AP1 missense rare variants
| Autor: | Sandhya Parkash, Dianna M. Milewicz, Dongchuan Guo, Callie S. Kwartler, Isabella Ciuffetelli Alamo, Rana O. Afifi, Ellen Regalado, Andrea Rideout |
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| Rok vydání: | 2019 |
| Předmět: |
Heart Defects
Congenital Male Pathology medicine.medical_specialty Computed Tomography Angiography Mutation Missense Arterial Occlusive Diseases Cell Cycle Proteins Compound heterozygosity Bone and Bones Cell Line Consanguinity Genetics Humans Medicine Missense mutation Genetic Predisposition to Disease Syndactyly Genetic Association Studies Genetics (clinical) business.industry Vascular disease Brachydactyly Homozygote Grange syndrome medicine.disease Penetrance Stenosis Hypertension Female Tomography X-Ray Computed business Transcription Factors |
| Zdroj: | American Journal of Medical Genetics Part A. 179:2500-2505 |
| ISSN: | 1552-4833 1552-4825 |
| Popis: | Grange syndrome (OMIM 602531) is an autosomal recessive condition characterized by severe early onset vascular occlusive disease and variable penetrance of brachydactyly, syndactyly, bone fragility, and learning disabilities. Grange syndrome is caused by homozygous or compound heterozygous loss-of-function variants in the YYA1P1 gene. We report on the case of a 53-year old female with novel homozygous missense variants in YYA1P1 (c.1079C>T, p.Pro360Leu), presenting with a history of brachysyndactyly, hypertension, and ischemic stroke. Imaging studies revealed stenosis of the bilateral internal carotid with extensive collateralization of cerebral vessels in a moyamoya-like pattern, along with stenosis in the splenic, common hepatic, celiac, left renal, and superior mesenteric arteries. Functional studies conducted with the patient's dermal fibroblasts suggest that the p.Pro360Leu variant decreases the stability of the YY1AP1 protein. This is the first report of a missense variant associated with Grange syndrome characterized by later onset of vascular disease and a lack of developmental delay and bone fragility. |
| Databáze: | OpenAIRE |
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