Late-onset dyshormonogenic goitrous hypothyroidism due to a homozygous mutation of the SLC26A7 gene: a case report.
SLC26A7 gene
Case report
Congenital hypothyroidism
Dyshormonogenic goiter
Genetic analysis
Journal
Italian journal of pediatrics
ISSN: 1824-7288
Titre abrégé: Ital J Pediatr
Pays: England
ID NLM: 101510759
Informations de publication
Date de publication:
29 May 2024
29 May 2024
Historique:
received:
08
08
2023
accepted:
06
05
2024
medline:
30
5
2024
pubmed:
30
5
2024
entrez:
29
5
2024
Statut:
epublish
Résumé
In this study, we used targeted next-generation sequencing (NGS) to investigate the genetic basis of congenital hypothyroidism (CH) in a 19-year-old Tunisian man who presented with severe hypothyroidism and goiter. The propositus reported the appearance of goiter when he was 18. Importantly, he did not show signs of mental retardation, and his growth was proportionate. A partial organification defect was detected through the perchlorate-induced iodide discharge test. NGS identified a novel homozygous mutation in exon 18 of the SLC26A7 gene (P628Qfs*11), which encodes for a new iodide transporter. This variant is predicted to result in a truncated protein. Notably, the patient's euthyroid brother was heterozygous for the same mutation. No renal acid-base abnormalities were found and the administration of 1 mg of iodine failed to correct hypothyroidism. We described the first case of goitrous CH due to a homozygous mutation of the SLC26A7 gene diagnosed during late adolescence.
Sections du résumé
BACKGROUND
BACKGROUND
In this study, we used targeted next-generation sequencing (NGS) to investigate the genetic basis of congenital hypothyroidism (CH) in a 19-year-old Tunisian man who presented with severe hypothyroidism and goiter.
CASE PRESENTATION
METHODS
The propositus reported the appearance of goiter when he was 18. Importantly, he did not show signs of mental retardation, and his growth was proportionate. A partial organification defect was detected through the perchlorate-induced iodide discharge test. NGS identified a novel homozygous mutation in exon 18 of the SLC26A7 gene (P628Qfs*11), which encodes for a new iodide transporter. This variant is predicted to result in a truncated protein. Notably, the patient's euthyroid brother was heterozygous for the same mutation. No renal acid-base abnormalities were found and the administration of 1 mg of iodine failed to correct hypothyroidism.
CONCLUSIONS
CONCLUSIONS
We described the first case of goitrous CH due to a homozygous mutation of the SLC26A7 gene diagnosed during late adolescence.
Identifiants
pubmed: 38812002
doi: 10.1186/s13052-024-01672-3
pii: 10.1186/s13052-024-01672-3
doi:
Substances chimiques
Sulfate Transporters
0
SLC26A7 protein, human
0
Antiporters
0
Types de publication
Case Reports
Journal Article
Langues
eng
Sous-ensembles de citation
IM
Pagination
106Informations de copyright
© 2024. The Author(s).
Références
Grasberger H, Refetoff S. Genetic causes of congenital hypothyroidism due to dyshormonogenesis. Curr Opin Pediatr. 2011;23(4):421–8. https://doi.org/10.1097/MOP.0b013e32834726a4 .
doi: 10.1097/MOP.0b013e32834726a4
pubmed: 21543982
pmcid: 3263319
Targovnik HM, Citterio CE, Rivolta CM. Iodide handling disorders (NIS, TPO, TG, IYD). Best Pract Res Clin Endocrinol Metab. 2017;31(2):195–212. https://doi.org/10.1016/j.beem.2017.03.006 .
doi: 10.1016/j.beem.2017.03.006
pubmed: 28648508
De Marco G, Agretti P, Montanelli L, Di Cosmo C, Bagattini B, De Servi M, Ferrarini E, Dimida A, Freitas Ferreira AC, Molinaro A, Ceccarelli C, Brozzi F, Pinchera A, Vitti P, Tonacchera M. Identification and functional analysis of novel dual oxidase 2 (DUOX2) mutations in children with congenital or subclinical hypothyroidism. J Clin Endocrinol Metab. 2011;96(8):E1335–9. https://doi.org/10.1210/jc.2010-2467 .
doi: 10.1210/jc.2010-2467
pubmed: 21565790
Petrovic S, Barone S, Xu J, Conforti L, Ma L, Kujala M, Kere J, Soleimani M. SLC26A7: a basolateral Cl-/HCO3- exchanger specific to intercalated cells of the outer medullary collecting duct. Am J Physiol Renal Physiol. 2004;286(1):F161–9. https://doi.org/10.1152/ajprenal.00219.2003 .
doi: 10.1152/ajprenal.00219.2003
pubmed: 12965893
Petrovic S, Ju X, Barone S, Seidler U, Alper SL, Lohi H, Kere J, Soleimani M. Identification of a basolateral Cl-/HCO3- exchanger specific to gastric parietal cells. Am J Physiol Gastrointest Liver Physiol. 2003;284(6):G1093–103. https://doi.org/10.1152/ajpgi.00454.2002 .
doi: 10.1152/ajpgi.00454.2002
pubmed: 12736153
Kosiek O, Busque SM, Föller M, Shcheynikov N, Kirchhoff P, Bleich M, Muallem S, Geibel JP. SLC26A7 can function as a chloride-loading mechanism in parietal cells. Pflugers Arch. 2007;454(6):989–98. https://doi.org/10.1007/s00424-007-0254-y .
doi: 10.1007/s00424-007-0254-y
pubmed: 17404755
Xu J, Song P, Nakamura S, Miller M, Barone S, Alper SL, Riederer B, Bonhagen J, Arend LJ, Amlal H, Seidler U, Soleimani M. Deletion of the chloride transporter slc26a7 causes distal renal tubular acidosis and impairs gastric acid secretion. J Biol Chem. 2009;284(43):29470–9. https://doi.org/10.1074/jbc.M109.044396 .
doi: 10.1074/jbc.M109.044396
pubmed: 19723628
pmcid: 2785580
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(20):e99631. https://doi.org/10.1172/jci.insight.99631 .
doi: 10.1172/jci.insight.99631
pubmed: 30333321
pmcid: 6237461
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. https://doi.org/10.1038/s42003-019-0503-6 .
doi: 10.1038/s42003-019-0503-6
pubmed: 31372509
pmcid: 6656751
Zou M, Alzahrani AS, Al-Odaib A, Alqahtani M, 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(5):1889–98. https://doi.org/10.1210/jc.2017-02202 .
doi: 10.1210/jc.2017-02202
pubmed: 29546359
Agretti P, De Marco G, Di Cosmo C, Ferrarini E, Montanelli L, Bagattini B, Vitti P, Tonacchera M. Congenital hypothyroidism caused by a novel homozygous mutation in the thyroglobulin gene. Eur J Pediatr. 2013;172(7):959–64. https://doi.org/10.1007/s00431-013-1976-9 .
doi: 10.1007/s00431-013-1976-9
pubmed: 23455760
Stoupa A, Kariyawasam D, Polak M, Carré A. Genetics of congenital hypothyroidism: Modern concepts. Pediatr Investig. 2022;6(2):123–34. https://doi.org/10.1002/ped4.12324 .
doi: 10.1002/ped4.12324
pubmed: 35774517
pmcid: 9218988
Yamaguchi T, Nakamura A, Nakayama K, Hishimura N, Morikawa S, Ishizu K, Tajima T. Targeted Next-generation sequencing for congenital hypothyroidism with positive neonatal TSH screening. J Clin Endocrinol Metab. 2020;105(8):dgaa308. https://doi.org/10.1210/clinem/dgaa308 .
doi: 10.1210/clinem/dgaa308
pubmed: 32459320
Bernal Barquero CE, Geysels RC, Jacques V, Carro GH, Martín M, Peyret V, Abregú MC, Papendieck P, Masini-Repiso AM, Savagner F, Chiesa AE, Citterio CE, Nicola JP. Targeted next-generation sequencing of congenital hypothyroidism-causative genes reveals unexpected thyroglobulin gene variants in patients with iodide transport defect. Int J Mol Sci. 2022;23(16):9251. https://doi.org/10.3390/ijms23169251 .
doi: 10.3390/ijms23169251
pubmed: 36012511
pmcid: 9409291
Fu C, Luo S, Zhang Y, Fan X, D’Gama AM, Zhang X, Zheng H, Su J, Li C, Luo J, Agrawal PB, Li Q, Chen S. Chromosomal microarray and whole exome sequencing identify genetic causes of congenital hypothyroidism with extra-thyroidal congenital malformations. Clin Chim Acta. 2019;489:103–8. https://doi.org/10.1016/j.cca.2018.11.035 .
doi: 10.1016/j.cca.2018.11.035
pubmed: 30508507
Nettore IC, Desiderio S, De Nisco E, Cacace V, Albano L, Improda N, Ungaro P, Salerno M, Colao A, Macchia PE. High-resolution melting analysis (HRM) for mutational screening of Dnajc17 gene in patients affected by thyroid dysgenesis. J Endocrinol Invest. 2018;41(6):711–7. https://doi.org/10.1007/s40618-017-0795-7 .
doi: 10.1007/s40618-017-0795-7
pubmed: 29159607
Tonacchera M, De Marco G, Agretti P, Montanelli L, Di Cosmo C, Freitas Ferreira AC, Dimida A, Ferrarini E, Ramos HE, Ceccarelli C, Brozzi F, Pinchera A, Vitti P. Identification and functional studies of two new dual-oxidase 2 (DUOX2) mutations in a child with congenital hypothyroidism and a eutopic normal-size thyroid gland. J Clin Endocrinol Metab. 2009;94(11):4309–14. https://doi.org/10.1210/jc.2009-0426 .
doi: 10.1210/jc.2009-0426
pubmed: 19789206