دورية أكاديمية
Targeted next-generation sequencing identifies a homozygous nonsense mutation in ABHD12, the gene underlying PHARC, in a family clinically diagnosed with Usher syndrome type 3
| العنوان: | Targeted next-generation sequencing identifies a homozygous nonsense mutation in ABHD12, the gene underlying PHARC, in a family clinically diagnosed with Usher syndrome type 3 |
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| المؤلفون: | Eisenberger Tobias, Slim Rima, Mansour Ahmad, Nauck Markus, Nürnberg Gudrun, Nürnberg Peter, Decker Christian, Dafinger Claudia, Ebermann Inga, Bergmann Carsten, Bolz Hanno |
| المصدر: | Orphanet Journal of Rare Diseases, Vol 7, Iss 1, p 59 (2012) |
| بيانات النشر: | BMC, 2012. |
| سنة النشر: | 2012 |
| المجموعة: | LCC:Medicine |
| مصطلحات موضوعية: | Usher syndrome, Deafness, Retinitis pigmentosa, ABHD12, PHARC, Medicine |
| الوصف: | Abstract Background Usher syndrome (USH) is an autosomal recessive genetically heterogeneous disorder with congenital sensorineural hearing impairment and retinitis pigmentosa (RP). We have identified a consanguineous Lebanese family with two affected members displaying progressive hearing loss, RP and cataracts, therefore clinically diagnosed as USH type 3 (USH3). Our study was aimed at the identification of the causative mutation in this USH3-like family. Methods Candidate loci were identified using genomewide SNP-array-based homozygosity mapping followed by targeted enrichment and next-generation sequencing. Results Using a capture array targeting the three identified homozygosity-by-descent regions on chromosomes 1q43-q44, 20p13-p12.2 and 20p11.23-q12, we identified a homozygous nonsense mutation, p.Arg65X, in ABHD12 segregating with the phenotype. Conclusion Mutations of ABHD12, an enzyme hydrolyzing an endocannabinoid lipid transmitter, cause PHARC (polyneuropathy, hearing loss, ataxia, retinitis pigmentosa, and early-onset cataract). After the identification of the ABHD12 mutation in this family, one patient underwent neurological examination which revealed ataxia, but no polyneuropathy. ABHD12 is not known to be related to the USH protein interactome. The phenotype of our patient represents a variant of PHARC, an entity that should be taken into account as differential diagnosis for USH3. Our study demonstrates the potential of comprehensive genetic analysis for improving the clinical diagnosis. |
| نوع الوثيقة: | article |
| وصف الملف: | electronic resource |
| اللغة: | English |
| تدمد: | 1750-1172 44832109 |
| العلاقة: | http://www.ojrd.com/content/7/1/59Test; https://doaj.org/toc/1750-1172Test |
| DOI: | 10.1186/1750-1172-7-59 |
| الوصول الحر: | https://doaj.org/article/e2f4483210944afc8241d9b2871bc3f1Test |
| رقم الانضمام: | edsdoj.2f4483210944afc8241d9b2871bc3f1 |
| قاعدة البيانات: | Directory of Open Access Journals |
Full Text Finder | تدمد: | 17501172 44832109 |
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| DOI: | 10.1186/1750-1172-7-59 |