Phenotypes associated with replacement of His by Arg in the Pendred syndrome gene.
BACKGROUND
Pendred syndrome is often associated with inner ear malformations, especially enlarged vestibular aqueduct (EVA). Recently, mutations in the Pendred syndrome gene (PDS) have been reported in patients with EVA, in addition to those with classical Pendred syndrome.


OBJECTIVE
The aim of this study was to investigate the genotype-phenotype correlations of PDS.


METHODS
Each of the 21 exons and flanking splice regions of PDS was analysed by direct DNA sequencing in nine patients with EVA; allele-specific amplification was performed to confirm the mutation. Genetic analyses were compared with thyroid function tests, perchlorate discharge tests, thyroid volume and pure-tone audiogram. Magnetic resonance imaging was used to determine the volume of the endolymphatic duct and sac of each patient.


RESULTS
A missense mutation, H723R, was identified in the homozygous state in three patients and in the heterozygous state in another three. Although none of the patients had goitre, increased serum thyroglobulin and an abnormal degree of iodide release were correlated with the number of mutant alleles identified. However, there was no relationship between the degree of hearing loss and the number of mutant alleles.


CONCLUSIONS
The present study reveals that the number of mutant alleles correlates with the degree of subclinical thyroid abnormality, but not with the degree of hearing loss in Japanese patients with the PDS missense mutation H723R.
Sato
E
E
Department of Otorhinolarngology, Nagoya University School of Medicine, 466-8550 Nagoya, Japan. eisuke@med.nagoya-u.ac.jp
Nakashima
T
T
Miura
Y
Y
Furuhashi
A
A
Nakayama
A
A
Mori
N
N
Murakami
H
H
Naganawa
S
S
Tadokoro
M
M
D000293:Adolescent; D000328:Adult; D000483:Alleles; D019943:Amino Acid Substitution; D001120:Arginine; D002352:Carrier Proteins / Q000235:genetics*; D002648:Child; D004711:Endolymphatic Duct / Q000473:pathology; D004712:Endolymphatic Sac / Q000473:pathology; D005260:Female; D006042:Goiter / Q000150:complications / Q000235:genetics*; D006319:Hearing Loss, Sensorineural / Q000150:complications / Q000235:genetics*; D006579:Heterozygote; D006639:Histidine; D006720:Homozygote; D006801:Humans; D007454:Iodides / Q000097:blood; D007455:Iodine / Q000378:metabolism*; D008279:Magnetic Resonance Imaging; D008297:Male; D026901:Membrane Transport Proteins; D009154:Mutation; D020125:Mutation, Missense; D010641:Phenotype; D012326:RNA Splicing; D017422:Sequence Analysis, DNA; D000076988:Sulfate Transporters; D013577:Syndrome; D013954:Thyroglobulin / Q000097:blood; D014723:Vestibular Aqueduct / Q000002:abnormalities / Q000473:pathology
D002352:Carrier Proteins; D007454:Iodides; D026901:Membrane Transport Proteins; C085609:SLC26A4 protein, human; D000076988:Sulfate Transporters; D006639:Histidine; D013954:Thyroglobulin; D001120:Arginine; D007455:Iodine