Novel COL4A1 mutations associated with HANAC syndrome: A role for the triple helical CB3[IV] domain
| Autor: | Florian Gekeler, Sonia Alamowitch, Béatrice Marro, Pierre Ronco, Emmanuelle Plaisier, Safa Benhassine, Michel Paques, Zhiyong Chen, Karine Dahan |
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| Rok vydání: | 2010 |
| Předmět: |
Adult
Collagen Type IV Male Pathology medicine.medical_specialty Biology Angiopathy Nephropathy 03 medical and health sciences Type IV collagen 0302 clinical medicine Genetics medicine Animals Humans Missense mutation Abnormalities Multiple Amino Acid Sequence Gene Conserved Sequence Genetics (clinical) 030304 developmental biology Brain Diseases 0303 health sciences Sequence Homology Amino Acid Raynaud Disease Anatomy Middle Aged medicine.disease Porencephaly Phenotype Pedigree 3. Good health Mutation Female medicine.symptom Sequence Alignment 030217 neurology & neurosurgery Muscle cramp |
| Zdroj: | American Journal of Medical Genetics Part A; Vol 152A American Journal of Medical Genetics Part A |
| ISSN: | 1552-4825 |
| Popis: | The COL4A1 gene encodes the α1-chain of type IV collagen, which is ubiquitously expressed in basement membranes. Mutations in COL4A1 have been reported in autosomal-dominant porencephaly and in patients with symptomatic small vessel brain disease, inconstantly associated with eye defects. We have previously reported three COL4A1 mutations associated with a systemic phenotype that we called HANAC (Hereditary Angiopathy, Nephropathy, Aneurysms, and Cramps). We carried out a clinical and genetic study of three families presenting with characteristic features of HANAC syndrome. Common systemic signs included arterial retinal tortuosity and muscle cramps, with a variable combination of small vessel brain disease, Raynaud phenomena, and kidney defects. Three novel COL4A1 missense substitutions are described, which affect highly conserved glycine residues within the collagenous domain of the protein. All six known mutations associated with the HANAC phenotype are localized within the CB3[IV] fragment of COL4A1, which encompasses major integrin-binding sites. Our results confirm that HANAC syndrome is a distinct clinical entity within the COL4A1-related disorders, which is characterized by systemic involvement and usually asymptomatic brain disease. The restricted distribution of COL4A1 mutations within the CB3[IV] region is a characteristic of the reports of patients with HANAC, which suggests that abnormal cell-type IV collagen interactions may underlie the systemic defects observed in this syndrome. |
| Databáze: | OpenAIRE |
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