Pendred syndrome among patients with congenital hypothyroidism detected by neonatalscreening: identification of two novel PDS/SLC26A4 mutations

Banghová, Karolína; Taji, Eva Al; Cinek, Ondřej; Novotná, Dana; Pourová, Radka Kremlíková; Zapletalová, Jiřina; Hníková, O; Lebl, Jan

doi:10.1007/s00431-007-0588-7

Cited by 34 publications

(14 citation statements)

References 31 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…As only one patient of three which had NTH was found to have biallelic SLC26A4 mutations we assume that, in agreement to a previous study (Banghova et al, 2008), this finding shows that NTH is rather a rare clinical manifestation of PS.…”

Section: Genotype -Phenotype Correlationsupporting

confidence: 91%

Spectrum and Frequency of SLC26A4 Mutations Among Czech Patients with Early Hearing Loss with and without Enlarged Vestibular Aqueduct (EVA)

Pourová

Janoušek²,

Jurovčík³

et al. 2010

Annals of Human Genetics

View full text Add to dashboard Cite

SummaryMutations in SLC26A4 cause Pendred syndrome (PS) -hearing loss with goitre -or DFNB4 -non-syndromic hearing loss (NSHL) with inner ear abnormalities such as Enlarged Vestibular Aqueduct (EVA) or Mondini Dysplasia (MD). We tested 303 unrelated Czech patients with early hearing loss (298 with NSHL and 5 with PS), all GJB2-negative, for SLC26A4 mutations and evaluated their clinical and radiological phenotype. Among 115 available HRCT/MRI scans we detected three MD (2.6%), three Mondini-like affections (2.6%), 16 EVA (13 bilateral -19.2% and 15.6% respectively) and 61 EVA/MD-negative scans (73.4%). We found mutation(s) in 26 patients (8.6%) and biallelic mutations in eight patients (2.7%) out of 303 tested. In 18 of 26 (69%) patients, no second mutation could be detected even using MLPA. The spectrum of SLC26A4 mutations in Czech patients is broad without any prevalent mutation. We detected 21 different mutations (four novel). The most frequent mutations were p.Val138Phe and p.Leu445Trp (18% and 8.9% of pathogenic alleles respectively). Among 13 patients with bilateral EVA, six patients (50%) carry biallelic mutations. In EVA -negative patients no biallelic mutations were found but 4.9% had monoallelic mutations. SLC26A4 mutations are present mostly in patients with EVA/MD and/or progressive HL and those with affected siblings.

show abstract

Section: Genotype -Phenotype Correlationsupporting

confidence: 91%

Spectrum and Frequency of SLC26A4 Mutations Among Czech Patients with Early Hearing Loss with and without Enlarged Vestibular Aqueduct (EVA)

Pourová

Janoušek²,

Jurovčík³

et al. 2010

Annals of Human Genetics

View full text Add to dashboard Cite

show abstract

“…PDS is rarely detected by neonatal screening for congenital hypothyroidism [9]. Rather, patients present because of severe congenital deafness.…”

Section: Defect In Apical Iodide Efflux Due To Mutations In the Slc26mentioning

confidence: 99%

Genetic causes of congenital hypothyroidism due to dyshormonogenesis

Grasberger

Refetoff

2011

Current Opinion in Pediatrics

188

123

View full text Add to dashboard Cite

Purpose of Review Overview of congenital hypothyroidism (CH) caused by thyroid hormone synthesis defects, the current understanding of their pathophysiology, and clinical implications of molecular diagnoses. Recent Findings Genetic defects in all known thyroid-specific factors required for thyroid hormone synthesis have been described. These include defects in iodide trapping (NIS), in the facilitated iodide efflux across the apical membrane (PDS), the organification of iodide within the follicular lumen (TPO, DUOX2, DUOXA2), the substrate for thyroid hormone synthesis (TG) and the ability to recover and retain intrathyroidal iodine (IYD). Clinical and biochemical evaluation aids in selecting the most appropriate candidate gene(s). A definite molecular diagnosis of thyroid dyshormonogenesis allows genetic counselling, and has prognostic value in differentiating transient from permanent CH and predicting the response of patients to iodine supplementation as adjunct or alternative treatment to L-T4 replacement. Summary CH due to thyroid dyshormonogenesis is a heterogenic disorder that may be caused by mutations in any of the known steps in the thyroid hormone biosynthesis pathway. An exact molecular diagnosis allows genetic counselling, the identification of asymptomatic mutation carriers at risk of recurrent hypothyroidism, and provides a rationale for adjunct iodide supplementation.

show abstract

“…For the endocrinological section it is important that the disease is one of the genetic causes of congenital hypothyroidism based on dyshormonogenesis 13 . However, the diagnostic difficulty lies in the very high phenotypic variability, especially of the thyroid involvement in the disease.…”

Section: Discussionmentioning

confidence: 99%

Thyroidectomy in a Patient with Multinodular Dyshormonogenetic Goitre - A Case of Pendred Syndrome Confirmed by Mutations in the PDS/SLC26A4 Gene

Banghová

Cinek²,

Taji³

et al. 2008

Journal of Pediatric Endocrinology and Metabolism

View full text Add to dashboard Cite

We report a young woman with genetically confirmed Pendred syndrome and discuss the current therapeutic strategies of dyshormonogenetic goitre. A small diffuse thyroid enlargement developed during infancy and although substitution therapy with L-thyroxine was adequate, it progressed and underwent multinodular transformation. Cervical ultrasound at the age of 22 years demonstrated three solid nodules and fine-needle aspiration biopsy showed a finding typical of follicular adenoma. It is known that dyshormonogenetic goitres have a tendency to grow despite appropriate treatment with L-thyroxine. Management of a patient with Pendred syndrome requires careful follow-up and regular imaging of the thyroid. Although the therapeutic approach to dyshormonogenetic goitres is still controversial, in our patient we chose total thyroidectomy as the most advantageous method to prevent the development of malignancies that may arise more frequently from dyshormonogenetic goitres than from goitres of other aetiologies.

show abstract

Pendred syndrome among patients with congenital hypothyroidism detected by neonatalscreening: identification of two novel PDS/SLC26A4 mutations

Cited by 34 publications

References 31 publications

Spectrum and Frequency of SLC26A4 Mutations Among Czech Patients with Early Hearing Loss with and without Enlarged Vestibular Aqueduct (EVA)

Spectrum and Frequency of SLC26A4 Mutations Among Czech Patients with Early Hearing Loss with and without Enlarged Vestibular Aqueduct (EVA)

Genetic causes of congenital hypothyroidism due to dyshormonogenesis

Thyroidectomy in a Patient with Multinodular Dyshormonogenetic Goitre - A Case of Pendred Syndrome Confirmed by Mutations in the PDS/SLC26A4 Gene

Contact Info

Product

Resources

About