Identification of recurrent c.742G>T nonsense mutation in ECM1 in Pakistani families suffering from lipoid proteinosis
| العنوان: | Identification of recurrent c.742G>T nonsense mutation in ECM1 in Pakistani families suffering from lipoid proteinosis |
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| المؤلفون: | Asif Mir, Amir Latif, Abdul Hameed, Nafees Ahmad, Muhammad Nasir, Christian M. K. Sieber, Salman Akbar Malik, Simeen Ber Rahman |
| المصدر: | Molecular Biology Reports. 41:2085-2092 |
| بيانات النشر: | Springer Science and Business Media LLC, 2014. |
| سنة النشر: | 2014 |
| مصطلحات موضوعية: | Adult, Male, Models, Molecular, Candidate gene, Adolescent, Protein Conformation, DNA Mutational Analysis, Molecular Sequence Data, Nonsense mutation, Locus (genetics), Biology, Young Adult, Exon, symbols.namesake, Extracellular matrix protein 1, Mutant protein, Genetics, medicine, Humans, Pakistan, Amino Acid Sequence, education, Molecular Biology, Skin, Sanger sequencing, Extracellular Matrix Proteins, education.field_of_study, Genodermatosis, General Medicine, medicine.disease, Pedigree, Phenotype, Codon, Nonsense, symbols, Lipoid Proteinosis of Urbach and Wiethe, Female, Sequence Alignment |
| الوصف: | Lipoid proteinosis (LP) is one of the rare, recessive autosomal disorders clinically characterized by widespread deposition of hyaline-like material in the skin, mucosa and viscera. Classical features include beaded eyelid papules, laryngeal infiltration and hoarseness of voice caused by pathogenic mutations in the ECM1gene located on 1q21.2. In present study ethnically different, three consanguineous Pakistani families with typical cutaneous features of LP were analysed to investigate the underlying molecular basis. PCR based linkage analysis using microsatellite markers localized the families to locus 1q21.2, harboring ECM1 gene. To identify the mutation in the candidate gene (ECM1), Sanger sequencing was carried out. All the families were found to carry c.742 G>T nonsense mutation in exon 7 of the ECM1 gene that resulted in a truncated ECM1 protein containing 247 amino acids instead of 540 (p.E248X). To further investigate the impact and importance of mutation in LP pathogenesis we applied different bioinformatics tools. In silico studies has predicted lack of functional domains and 65 % shorter ECM1 mutant protein. It is the first report of recurrence mutation from Pakistan as c.742G>T nonsense mutation was found in three ethnically different Pakistani families with LP. Study strengthens the conclusion that c.742G>T mutation is the pathological cause of LP. Furthermore, data also support the fact that exon 7 is one of the most common hot spots of pathological mutations in ECM1. The absence of functional domains and truncated sequence most likely contribute to the lack of ECM1 function and thereby influence several aspects of dermal homeostasis that leads to LP pathogenesis. |
| تدمد: | 1573-4978 0301-4851 |
| الوصول الحر: | https://explore.openaire.eu/search/publication?articleId=doi_dedup___::0841c7cfee193e215b3e99321adec7aeTest https://doi.org/10.1007/s11033-014-3057-1Test |
| حقوق: | CLOSED |
| رقم الانضمام: | edsair.doi.dedup.....0841c7cfee193e215b3e99321adec7ae |
| قاعدة البيانات: | OpenAIRE |
| تدمد: | 15734978 03014851 |
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