Mutation analysis of Netrin 1 and HMX3 genes in patients with superior semicircular canal dehiscence syndrome.

Abstract

CONCLUSION:

In spite of its absence in the control population, there is questionable evidence for the alteration c.114C->T in the HMX3 gene being implicated in the development of superior semicircular canal dehiscence (SSCD). However, the concept of a complex disease is valid for SSCD and a possible molecular origin can neither be confirmed nor excluded by the results of this study.

OBJECTIVES:

SSCD was first described in 1998 by Minor et al. While the etiology is not clear, findings from both temporal bone CT and histologic studies suggest a congenital or developmental origin. In recent years, a couple of genes regulating inner ear morphogenesis have been described. Specifically, Netrin-1 and HMX3 have been shown to be critically involved in the formation of the SCC. Molecular alterations in these two genes might lead to a disturbed development of this canal and might represent an explanation for SSCD.

METHODS:

DNA was extracted from whole blood of 15 patients with SSCD. The coding sequences of Netrin-1 and HMX3 were amplified by PCR and sequenced.

RESULTS:

One sequence alteration, heterozygous c.114C->T (conservative change without alteration of amino acid) in exon 1 of HMX3, was detected in 2 of 15 patients but not in 300 control chromosomes. The study was supported in part by the Emilia-Guggenheim-Schnurr-Foundation, Basel, Switzerland.

• Authors: Nikola Roknic, Alexander Huber, Stefan C A Hegemann, Rudolf Häusler, Nicolas Gürtler
• Journal: Acta oto-laryngologica (Acta Otolaryngol) Vol. 132 Issue 10 Pg. 1061-5 (Oct 2012) ISSN: 1651-2251 [Electronic] England
• PMID: 22779713 (Publication Type: Comparative Study, Journal Article)

Chemical References

• HMX3 protein, human
• Homeodomain Proteins
• NTN1 protein, human
• Nerve Growth Factors
• Tumor Suppressor Proteins
• Netrin-1

Topics

• Adult
• Aged
• Cohort Studies
• DNA Mutational Analysis
• Female
• Genetic Predisposition to Disease
• Homeodomain Proteins (genetics)
• Humans
• Labyrinth Diseases (diagnostic imaging, genetics)
• Male
• Middle Aged
• Mutation
• Nerve Growth Factors (genetics)
• Netrin-1
• Semicircular Canals (abnormalities, diagnostic imaging)
• Sensitivity and Specificity
• Syndrome
• Temporal Bone (diagnostic imaging)
• Tomography, X-Ray Computed
• Tumor Suppressor Proteins (genetics)