ESPE Yearbook of Paediatric Endocrinology

Thyroid. 2020;30:1831–1833. doi: 10.1089/thy.2020.0293.

Every year, we report on new genes that have been associated with congenital hypothyroidism. But it is the first time in all these years that, following the first description, other groups from different continents confirm the first reports in independent cohorts in such a short time after publication.

This is the case for mutations in the SLC26A7 gene, first described by Cangul et al. in 2018 in six independent families from Pakistan, Turkey and Finland [1] and presented in the 2018 Yearbook chapter. The typical phenotype is congenital hypothyroidism with goiter, however goiter is not present in all patients. In this short period of time, four further publications described new cases in patients from Saudi-Arabia, Japan, Sudan [2-4] and Germany (the selected most recent publication).

This rapid progress may be explained by technical advances for mutational screening by next generation screening (NGS) over the last years, or by publication bias, but on the other hand, it might also suggest a relevant new genetic cause of disease, as Ishi et al. provided further mechanistic and functional data on the role of the SLC26A7 transporter as a new iodine transporter at the apical membrane of the thyrocytes [3]. Systematic genetic analyses by complete NGS panels for all known genes associated with congenital hypothyroidism integrating SLC26A7 will give precise incidence rates in different cohorts in the future. Until then, SLC26A7 is a strong new candidate gene in patients with congenital hypothyroidism due to thyroid dyshormonogenesis.

Reference: 1. Cangul H, Liao XH, Schoenmakers E, Kero J, Barone S, Srichomkwun P, Iwayama H, Serra EG, Saglam H, Eren E, Tarim O, Nicholas AK, Zvetkova I, Anderson CA, Frankl FEK, Boelaert K, Ojaniemi M, Jääskeläinen J, Patyra K, Löf C, Williams ED; UK10K Consortium, Soleimani M, Barrett T, Maher ER, Chatterjee VK, Refetoff S, Schoenmakers N. Homozygous loss-of-function mutations in SLC26A7 cause goitrous congenital hypothyroidism. JCI Insight. 2018;3:e99631. doi: 10.1172/jci.insight.99631.2. Zou M, Alzahrani AS, Al-Odaib A, Alqahtani MA, Babiker O, Al-Rijjal RA, BinEssa HA, Kattan WE, Al-Enezi AF, Al Qarni A, Al-Faham MSA, Baitei EY, Alsagheir A, Meyer BF, Shi Y. Molecular Analysis of Congenital Hypothyroidism in Saudi Arabia: SLC26A7 Mutation Is a Novel Defect in Thyroid Dyshormonogenesis. J Clin Endocrinol Metab. 2018;103:1889–1898. doi: 10.1210/jc.2017-02202.3. Ishii J, Suzuki A, Kimura T, Tateyama M, Tanaka T, Yazawa T, Arimasu Y, Chen IS, Aoyama K, Kubo Y, Saitoh S, Mizuno H, Kamma H. Congenital goitrous hypothyroidism is caused by dysfunction of the iodide transporter SLC26A7. Commun Biol. 2019;2:270. doi: 10.1038/s42003-019-0503-6. eCollection 2019.4. Bruellman RJ, Watanabe Y, Ebrhim RS, Creech MK, Abdullah MA, Dumitrescu AM, Refetoff S, Weiss RE. Increased Prevalence of TG and TPO Mutations in Sudanese Children With Congenital Hypothyroidism. J Clin Endocrinol Metab. 2020;105:1564–72. doi: 10.1210/clinem/dgz297.