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Homozygous loss-of-function mutations in SLC26A7 cause goitrous congenital hypothyroidism

Published on Oct 18, 2018in JCI insight6.014
· DOI :10.1172/jci.insight.99631
Hakan Cangul10
Estimated H-index: 10
,
Xiao Hui Liao30
Estimated H-index: 30
+ 24 AuthorsNadia Schoenmakers17
Estimated H-index: 17
Abstract
: Defects in genes mediating thyroid hormone biosynthesis result in dyshormonogenic congenital hypothyroidism (CH). Here, we report homozygous truncating mutations in SLC26A7 in 6 unrelated families with goitrous CH and show that goitrous hypothyroidism also occurs in Slc26a7-null mice. In both species, the gene is expressed predominantly in the thyroid gland, and loss of function is associated with impaired availability of iodine for thyroid hormone synthesis, partially corrected in mice by iodine supplementation. SLC26A7 is a member of the same transporter family as SLC26A4 (pendrin), an anion exchanger with affinity for iodide and chloride (among others), whose gene mutations cause congenital deafness and dyshormonogenic goiter. However, in contrast to pendrin, SLC26A7 does not mediate cellular iodide efflux and hearing in affected individuals is normal. We delineate a hitherto unrecognized role for SLC26A7 in thyroid hormone biosynthesis, for which the mechanism remains unclear.
  • References (23)
  • Citations (4)
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References23
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Cited By4
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#1Ryan J. Bruellman (UM: University of Miami)H-Index: 1
#2Yui Watanabe (UM: University of Miami)H-Index: 2
Last. E WeissRoy (UM: University of Miami)H-Index: 53
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CONTEXT: Congenital hypothyroidism (CH) is due to dyshormonogenesis in 10% to 15% of subjects worldwide but accounts for 60% of CH cases in the Sudan. OBJECTIVE: To investigate the molecular basis of CH in Sudanese families. DESIGN: Clinical phenotype reporting and serum thyroid hormone measurements. Deoxyribonucelic acid extraction for whole-exome sequencing and Sanger sequencing. SETTING: University research center. PATIENTS: Twenty-six Sudanese families with CH. INTERVENTION: Clinical evaluat...
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Abstract Acid-secreting intercalated cells of the collecting duct express the chloride/bicarbonate kidney anion exchanger 1 (kAE1) as well as SLC26A7, two proteins that colocalize in the basolateral membrane. The latter protein has been reported to function either as a chloride/bicarbonate exchanger or a chloride channel. Both kAE1 and SLC26A7 are detected in the renal medulla, an environment hyper-osmotic to plasma. Individuals with mutations in the SLC4A1 gene encoding kAE1 and mice lacking SL...
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#1Héctor M. Targovnik (UBA: University of Buenos Aires)H-Index: 27
#2Karen G. Scheps (UBA: University of Buenos Aires)H-Index: 3
Last. Carina M. Rivolta (UBA: University of Buenos Aires)H-Index: 18
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Abstract Primary congenital hypothyroidism (CH) is the most common endocrine disease in children and one of the most common preventable causes of both cognitive and motor deficits. CH is a heterogeneous group of thyroid disorders in which inadequate production of thyroid hormone occurs due to defects in proteins involved in the gland organogenesis (dysembryogenesis) or in multiple steps of thyroid hormone biosynthesis (dyshormonogenesis). Dysembryogenesis is associated with genes responsible for...
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#1Aminata Touré (CNRS: Centre national de la recherche scientifique)H-Index: 20
In mammals, sperm cells produced within the testis are structurally differentiated but remain immotile and are unable to fertilize the oocyte unless they undergo a series of maturation events during their transit in the male and female genital tracts. This post-testicular functional maturation is known to rely on the micro-environment of both male and female genital tracts, and is tightly controlled by the pH of their luminal milieus. In particular, within the epididymis, the establishment of a ...
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#1Jun Ishii (Dokkyo Medical University)H-Index: 8
#2Atsushi Suzuki (Nagoya City University)H-Index: 2
Last. Hiroshi Kanma (Kyorin University)H-Index: 16
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Iodide transport and storage in the thyroid follicles is crucial for thyroid hormone synthesis. Pendrin, the iodide exporter that transports iodide to thyroid follicles, is responsible for Pendred syndrome, a disorder characterized by congenital hypothyroidism and hearing loss. However, thyroid hormone levels are basically normal in patients with Pendred syndrome, indicating the presence of another unknown iodide transporter. Here, we show that SLC26A7 is a novel iodide transporter in the thyroi...
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#1Giuseppina Grieco (UCL: Université catholique de Louvain)H-Index: 3
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Last. Christophe E. Pierreux (UCL: Université catholique de Louvain)H-Index: 31
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BACKGROUND: The production of thyroid hormones (T3, T4) depends on the organization of the thyroid in follicles, which are lined by a monolayer of thyrocytes with strict apico-basal polarity. This polarization supports vectorial transport of thyroglobulin for storage into, and recapture from, the colloid. It also allows selective addressing of channels, transporters, ion pumps and enzymes to their appropriate basolateral (NIS, SLC26A7 and Na+/K+-ATPase) or apical membrane domain (Anoctamin, SLC2...
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