Genetic analyses in a cohort of Portuguese pediatric patients with congenital hypothyroidism
-
Rita Santos-Silva
,
Marta Rosário
Abstract
Background
Permanent primary congenital hypothyroidism (CH) can be caused by thyroid dysgenesis or dyshormonogenesis. A molecular genetic study is recommended in dyshormonogenesis, in syndromic hypothyroidism and when there is a family history of CH. The aim of this study was to identify a monogenic etiology for CH in selected individuals from a cohort of primary permanent CH.
Methods
From an initial cohort of 79 patients with permanent CH (3–19 years), 11 patients were selected for molecular analyses. Nine patients with dyshormonogenesis (normal in-situ gland or goiter) were screened for causative variants, by next-generation sequencing (NGS), in 28 genes known to be responsible for CH. One patient with a family history of CH was screened for the paired-box gene 8 (PAX8) gene and another patient with a syndromic CH was screened for the NKX2-1 gene.
Results
We found a monogenic basis of disease in eight patients, involving the thyroid peroxidase (TPO) gene (four patients), the thyroglobulin (TG) gene (two patients), and the PAX8 and NKX2-1 genes (one patient each). Two patients were heterozygotes, one harboring a variant in the TG gene and the other in the SLC5A5 gene. In one patient, we found no potential causative variants in any of the 28 genes screened. We described five novel variants: three in the TG gene, one in the NKX2-1 and one in the SLC5A5 gene, all of them classified as pathogenic.
Conclusions
In eight of the 11 screened patients, a monogenic disease was found. These results highlight the advantage of using an NGS panel and provide further data regarding the molecular basis of CH.
Author contributions: All the authors have accepted responsibility for the entire content of this submitted manuscript and approved submission.
Research funding: None declared.
Employment or leadership: None declared.
Honorarium: None declared.
Competing interests: This research did not receive any specific grant from funding agencies in the public, commercial or not-for-profit sectors.
Conflict of interest: The authors declare that they have no conflict of interest.
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©2019 Walter de Gruyter GmbH, Berlin/Boston
Artikel in diesem Heft
- Frontmatter
- Editorial
- Hypo- and hyperthyroidism in early life – new developments
- Letters to the Editor
- Optic nerve sheath diameter appraisal in children affected by diabetic ketoacidosis
- Optic nerve sheath diameter ultrasound measurement to evaluate cerebral edema in children with diabetic ketoacidosis
- Original Articles
- Novel ABCD1 gene mutations in Iranian pedigrees with X-linked adrenoleukodystrophy
- Phenylketonuric patients represent their disease
- Mapping of IDUA gene variants in Pakistani patients with mucopolysaccharidosis type 1
- Genetic testing of two Pakistani patients affected with rare autosomal recessive Fanconi-Bickel syndrome and identification of a novel SLC2A2 splice site variant
- Sex differences in infant body composition emerge in the first 5 months of life
- Characterization of the duration of treatment with diazoxide in infants with prolonged hyperinsulinism (PHI)
- Clinical, biochemical and gender characteristics of 97 prepubertal children with premature adrenarche
- The adjustment of 17-hydroxyprogesterone cut-off values for congenital adrenal hyperplasia neonatal screening by GSP according to gestational age and age at sampling
- The role of vitamin D replacement therapy in serum FGF23 concentration in children with myelomeningocele compared with healthy children – a preliminary study
- Genetic analyses in a cohort of Portuguese pediatric patients with congenital hypothyroidism
- Congenital hypothyroidism in preterm infants: a 3- to 8-year longitudinal study in southern Thailand
- Case Reports
- A case of PHACE syndrome with growth hormone deficiency and abnormal thyroid functions
- A novel DCAF17 homozygous mutation in a girl with Woodhouse-Sakati syndrome and review of the current literature
- Acquired von Willebrand’s syndrome caused by primary hypothyroidism in a 5-year-old girl
- Double variants in TSHR and DUOX2 in a patient with hypothyroidism: case report
Artikel in diesem Heft
- Frontmatter
- Editorial
- Hypo- and hyperthyroidism in early life – new developments
- Letters to the Editor
- Optic nerve sheath diameter appraisal in children affected by diabetic ketoacidosis
- Optic nerve sheath diameter ultrasound measurement to evaluate cerebral edema in children with diabetic ketoacidosis
- Original Articles
- Novel ABCD1 gene mutations in Iranian pedigrees with X-linked adrenoleukodystrophy
- Phenylketonuric patients represent their disease
- Mapping of IDUA gene variants in Pakistani patients with mucopolysaccharidosis type 1
- Genetic testing of two Pakistani patients affected with rare autosomal recessive Fanconi-Bickel syndrome and identification of a novel SLC2A2 splice site variant
- Sex differences in infant body composition emerge in the first 5 months of life
- Characterization of the duration of treatment with diazoxide in infants with prolonged hyperinsulinism (PHI)
- Clinical, biochemical and gender characteristics of 97 prepubertal children with premature adrenarche
- The adjustment of 17-hydroxyprogesterone cut-off values for congenital adrenal hyperplasia neonatal screening by GSP according to gestational age and age at sampling
- The role of vitamin D replacement therapy in serum FGF23 concentration in children with myelomeningocele compared with healthy children – a preliminary study
- Genetic analyses in a cohort of Portuguese pediatric patients with congenital hypothyroidism
- Congenital hypothyroidism in preterm infants: a 3- to 8-year longitudinal study in southern Thailand
- Case Reports
- A case of PHACE syndrome with growth hormone deficiency and abnormal thyroid functions
- A novel DCAF17 homozygous mutation in a girl with Woodhouse-Sakati syndrome and review of the current literature
- Acquired von Willebrand’s syndrome caused by primary hypothyroidism in a 5-year-old girl
- Double variants in TSHR and DUOX2 in a patient with hypothyroidism: case report
