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. CONCLUSION: 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.
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. CONCLUSION: 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.
Authors: H-J Park; S Shaukat; X-Z Liu; S H Hahn; S Naz; M Ghosh; H-N Kim; S-K Moon; S Abe; K Tukamoto; S Riazuddin; M Kabra; R Erdenetungalag; J Radnaabazar; S Khan; A Pandya; S-I Usami; W E Nance; E R Wilcox; S Riazuddin; A J Griffith Journal: J Med Genet Date: 2003-04 Impact factor: 6.318
Authors: Kelly A King; Byung Yoon Choi; Christopher Zalewski; Anne C Madeo; Ani Manichaikul; Shannon P Pryor; Anne Ferruggiaro; David Eisenman; H Jeffrey Kim; John Niparko; James Thomsen; John A Butman; Andrew J Griffith; Carmen C Brewer Journal: Laryngoscope Date: 2010-02 Impact factor: 3.325
Authors: Liuska Pesce; Aigerim Bizhanova; Juan Carlos Caraballo; Whitney Westphal; Maria L Butti; Alejandro Comellas; Peter Kopp Journal: Endocrinology Date: 2011-11-22 Impact factor: 4.736
Authors: F Bogazzi; D Russo; F Raggi; F Ultimieri; S Berrettini; F Forli; L Grasso; C Ceccarelli; S Mariotti; A Pinchera; L Bartalena; E Martino Journal: J Endocrinol Invest Date: 2004-05 Impact factor: 4.256