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


OBJECTIVE
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.
Klinik für Hals-Nasen-Ohrenkrankheiten, Hals- und Gesichtschirurgie, Kantonsspital Aarau AG, Switzerland.
Nikola
N
Roknic
Alexander
A
Huber
Stefan C A
SC
Hegemann
Rudolf
R
Häusler
Nicolas
N
Gürtler
D000328:Adult; D000368:Aged; D015331:Cohort Studies; D004252:DNA Mutational Analysis; D005260:Female; D020022:Genetic Predisposition to Disease; D018398:Homeodomain Proteins / Q000235:genetics*; D006801:Humans; D007759:Labyrinth Diseases / Q000000981:diagnostic imaging / Q000235:genetics*; D008297:Male; D008875:Middle Aged; D009154:Mutation; D009414:Nerve Growth Factors / Q000235:genetics*; D000075388:Netrin-1; D012665:Semicircular Canals / Q000002:abnormalities* / Q000000981:diagnostic imaging; D012680:Sensitivity and Specificity; D013577:Syndrome; D013701:Temporal Bone / Q000000981:diagnostic imaging; D014057:Tomography, X-Ray Computed; D025521:Tumor Suppressor Proteins / Q000235:genetics*
C578991:HMX3 protein, human; D018398:Homeodomain Proteins; C000617351:NTN1 protein, human; D009414:Nerve Growth Factors; D025521:Tumor Suppressor Proteins; D000075388:Netrin-1