Context: Pendred syndrome (PS) and (TPO) deficiency are autosomal-recessive disorders which result in thyroid dyshormonogenesis. They share congenital hypothyroidism, goiter, and a iodide organification defect as common features. While the hallmark of PS is sensorineural deafness, other forms of congenital hypothyroidism may also lead to hearing impairment. Therefore, a definite diagnosis may be difficult and require molecular genetic analyses.

Case report: The propositus presented at birth with primary hypothyroidism and goiter. He also had congenital bilateral moderate hearing loss and Pendred syndrome was suspected.

Methods: We sequenced the SLC26A4/PDS and TPO genes in the propositus and tested familial segregation of mutations in all available family members who were phenotypically normal. The functional consequences of the identified pendrin mutation (p.R776C) were studied in vitro.

Results: Sequencing of the SLC26A4/PDS gene revealed a single monoallelic missense mutation in the propositus (p.R776C). This mutation, which was inherited from his unaffected mother, has previously been identified in an individual with deafness and an enlarged vestibular aqueduct. Sequencing of the TPO gene revealed compound heterozygosity for a novel nonsense mutation (p.Q235X) and a known missense mutation (p.Y453D). The SLC26A4/PDS mutation p.R776C retained its ability to transport iodide in vitro.

Conclusions: These results show that the propositus carries three sequence variants in two genes: a monoallelic SLC26A4/PDS sequence variant and compound heterozygous TPO mutations. Our study illustrates that if only a single heterozygous SLC26A4/PDS mutation is found in a patient with goiter and deafness, other genetic explanations should be considered.