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A clinical description of a novel X-linked dominant hearing impairment in a five- generation family.
Uppsala University, Medicinska vetenskapsområdet, Faculty of Medicine, Department of Surgical Sciences.
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Manuscript (Other academic)
URN: urn:nbn:se:uu:diva-96368OAI: oai:DiVA.org:uu-96368DiVA: diva2:170921
Available from: 2007-11-01 Created: 2007-11-01 Last updated: 2010-01-13Bibliographically approved
In thesis
1. Clinical and Genetic Studies of Hearing Impairment
Open this publication in new window or tab >>Clinical and Genetic Studies of Hearing Impairment
2007 (English)Doctoral thesis, comprehensive summary (Other academic)
Abstract [en]

Monogenic disorders offer a possibility for studies of genetic disturbances in hearing impairment—a knowledge which could be essential for development of future treatment options. In this thesis, the underlying genetic disturbances in neurofibromatosis 2 (NF2) and familial Meniere’s disease (FMD) were evaluated, and familial X-linked hearing impairment was described from a clinical point of view.

In paper I, constitutional DNA from 116 individuals with NF2 of variable severity was studied using the array-CGH method focusing on a 7.6-Mb area surrounding the NF2 gene on chromosome 22q. Deletions were found in 20.7% of samples. In mild NF2, the deletions were small, but variable sizes of deletions were found in cases that were moderately or severely affected. Disease phenotype could not be predicted from the size of the deletions.

In papers II and III, a single five-generation family with autosomal dominant FMD was described. Anticipation concerning age of onset was observed. Genome scan revealed five candidate gene regions with a LOD score of > 1. Two additional families with autosomal dominant MD were analyzed for linkage to these five regions. A cumulative Zmax of 3.46 was obtained for a single 463-kb region on chromosome 12p12.3, containing only one known gene: PIK3C2G. This encodes a protein with a proposed role in hair cell regeneration in mammalian ears. No mutations were found in protein-coding sequences or exon-intron borders. In two of the three families, a shared haplotype, suggested common ancestry, was found to extend over 1.7 Mb, which could be a genomic region of importance for FMD.

In paper IV, a family in which five males displayed progressive low- and mid-frequency hearing impairment from the first or second decade was described. Female carriers were affected by a high-frequency hearing impairment from the fourth decade. The family could represent a novel X-linked dominant audiophenotype.

Place, publisher, year, edition, pages
Uppsala: Acta Universitatis Upsaliensis, 2007. 57 p.
Digital Comprehensive Summaries of Uppsala Dissertations from the Faculty of Medicine, ISSN 1651-6206 ; 286
Otorhinolaryngology, NF2, array-CGH, Meniere’s disease, PIK3C2G, X-linked, progressive, hearing impairment, Otorhinolaryngologi
urn:nbn:se:uu:diva-8290 (URN)978-91-554-7006-7 (ISBN)
Public defence
2007-11-23, Skoogsalen, 78.79, Öronkliniken, Akademiska Sjukhuset, 751 85, Uppsala, 09:00
Available from: 2007-11-01 Created: 2007-11-01 Last updated: 2011-06-28Bibliographically approved

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