Pendred syndrome among patients with congenital hypothyroidism detected by neonatalscreening: identification of two novel <Emphasis Type="Italic">PDS/SLC26A4</Emphasis> mutations |
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Authors: | Karolina Banghova Eva Al Taji Ondrej Cinek Dana Novotna Radka Pourova Jirina Zapletalova Olga Hnikova Jan Lebl |
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Institution: | (1) Department of Paediatrics, Second Faculty of Medicine, Charles University in Prague, Prague, Czech Republic;(2) Department of Paediatrics, Third Faculty of Medicine, Charles University in Prague, Prague, Czech Republic;(3) Second Department of Paediatrics, University Hospital, Brno, Czech Republic;(4) Department of Paediatrics, Faculty of Medicine, Palacky University, Olomouc, Czech Republic;(5) Department of Paediatrics, University Hospital Motol, V Uvalu 84, 150 06 Prague, Czech Republic |
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Abstract: | Pendred syndrome is an autosomal recessive disorder characterised by sensorineural hearing loss and thyroid dyshormonogenesis.
It is caused by mutations in the PDS/SLC26A4 gene (OMIM 605646) encoding for pendrin. Hypothyroidism in Pendred syndrome can be—although rarely—present from birth and
therefore diagnosed by neonatal screening. The aim of our study was to identify patients with Pendred syndrome among a historical
cohort of patients with congenital hypothyroidism (CH) identified by neonatal screening, and to find their mutations in the
PDS/SLC26A4 gene. We investigated 197 Czech Caucasian children with CH detected by the neonatal screening between the years 1985 and
2005. The clinical diagnosis of Pendred syndrome was based on the laboratory and sonographic signs of thyroid dyshormonogenesis
in association with sensorineural hearing loss. In subjects clinically diagnosed with Pendred syndrome, we sequenced all
exons and exon-intron boundaries of the PDS/SLC26A4 gene. Hearing loss was present in 10/197 children with screening-detected CH. Of these, three fulfilled the diagnostic criteria
of Pendred syndrome. Two patients were compound heterozygotes for PDS/SLC26A4 mutations: patient 1 carried c.2089+1G>A / c.3G>C and patient 2 carried p.Tyr530His / p.Val422Asp. Two of the four identified
mutations were novel (c.3G>C in patient 1 and p.Val422Asp in patient 2). The third patient was free of mutations in the PDS/SLC26A4 gene, representing a phenocopy. In conclusion, our results indicate the rarity of Pendred syndrome as a cause of CH. The
identification of two novel mutations expands the spectrum of mutations in the PDS/SLC26A4 gene and emphasizes their marked allelic heterogeneity.
The study was supported by grants of the Czech Ministry of Education (MSM 0021620814) and Charles University in Prague (GAUK
2008/2007). |
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Keywords: | Congenital hypothyroidism PDS SLC26A4 Pendrin Sensorineural hearing loss |
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