Thyroid Hypoplasia in Congenital Hypothyroidism Associated with Thyroid Peroxidase Mutations

被引:17
作者
Stoupa, Athanasia [1 ,2 ,3 ]
Chaabane, Rim [4 ]
Gueriouz, Manelle [2 ]
Raynaud-Ravni, Catherine [5 ]
Nitschke, Patrick [6 ]
Bole-Feysot, Christine [7 ]
Mnif, Mouna [8 ]
Ammar Keskes, Leila [4 ]
Hachicha, Mongia [9 ]
Belguith, Neila [4 ,10 ]
Polak, Michel [1 ,2 ,3 ,11 ,12 ]
Carre, Aurore [2 ,3 ]
机构
[1] Necker Childrens Univ Hosp, AP HP, Pediat Endocrinol Diabetol & Gynecol Dept, Paris, France
[2] IMAGINE Inst, INSERM, U1163, Paris, France
[3] Cochin Inst, INSERM, U1016, 123 Blvd Port Royal, F-75014 Paris, France
[4] Univ Sfax, Med Sch, Lab Human Mol Genet, Sfax, Tunisia
[5] St Etienne Univ Hosp, Pediat Endocrinol Dept, St Etienne, France
[6] IMAGINE Inst, INSERM, U1163, Bioinformat Platform, Paris, France
[7] IMAGINE Inst, INSERM, U1163, Genom Platform, Paris, France
[8] CHU Hedi Chaker, Dept Endocrinol, Sfax, Tunisia
[9] CHU Hedi Chaker, Dept Pediat, Sfax, Tunisia
[10] CHU Hedi Chaker, Dept Med Genet, Sfax, Tunisia
[11] Ctr Reference Malad Endocriniennes Rares Croissan, Rare Growth & Dev Dis Ctr, Paris, France
[12] Paris Descartes Univ, Sorbonne Paris Cite, Paris, France
关键词
congenital hypothyroidism; thyroid dysgenesis; dyshormonogenesis; thyroid peroxidase; whole exome sequencing; GENE; GOITER;
D O I
10.1089/thy.2017.0502
中图分类号
R5 [内科学];
学科分类号
1002 ; 100201 ;
摘要
Background: Primary congenital hypothyroidism (CH) affects about 1:3000 newborns worldwide and is mainly caused by defects in thyroid gland development (thyroid dysgenesis [TD]) or hormone synthesis. A genetic cause is identified in <10% of TD patients. The aim was to identify novel candidate genes in patients with TD using next-generation sequencing tools. Patient Findings: Whole exome sequencing was used to study two families: a consanguineous Tunisian family (one child with severe thyroid hypoplasia) and a French family (two newborn siblings, with a thyroid in situ that was not enlarged on ultrasound at diagnosis). Variants in candidate genes were filtered according to type of variation, frequency in public and in-house databases, in silico prediction tools, and inheritance mode. Unexpectedly, three different variants of the thyroid peroxidase (TPO) gene were identified. A homozygous missense mutation (c.875C>T, p.S292F) was found in the Tunisian patient with severe thyroid hypoplasia. The two French siblings were compound heterozygotes (c.387delC/c.2578G>A, p.N129Kfs*80/p.G860R) for TPO mutations. All three mutations have been previously described in patients with goitrous CH. In these patients, treatment was initiated immediately after diagnosis, and the effect, if any, of thyrotropin stimulation of these thyroids remains unclear. Conclusions: The first cases are reported of thyroid hypoplasia at diagnosis during the neonatal period in patients with CH and TPO mutations. These cases highlight the importance of screening for TPO mutations not only in goitrous CH, but also in normal or small-size thyroids, and they broaden the clinical spectrum of described phenotypes.
引用
收藏
页码:941 / 944
页数:4
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