Importance of molecular genetic analysis in the diagnosis and classification of congenital hypothyroidism

Targovnik, Héctor M.

doi:10.1007/s12020-013-0075-z

Cited by 2 publications

(2 citation statements)

References 10 publications

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“…Irrespective of biological CH severity, we also observed that goiter was mainly associated with familial TDH (56.7%) compared to infants negative for ACMG variant classes 3 to 5, as a relevant clinical sign to ask for a genetic investigation. As previously described, we identified that homozygous variants in TG , TPO, and SLC5A5 and oligogenicity were associated with goiter and severe CH whereas monoallelic variants in TSHR , TG , DUOX2, and TPO were related to milder phenotypes ( 21 , 22 ). Inactivating heterozygous TSHR variants were present in 10.8% (4/37 cases) of our TDH cases with a heterogeneous clinical presentation: CH severity was inconstant, especially for the hot spot variant Arg450His leading to both subclinical (F6) and severe CH (F15).…”

Section: Discussionsupporting

confidence: 65%

Next-Generation Sequencing Analysis Reveals Frequent Familial Origin and Oligogenism in Congenital Hypothyroidism With Dyshormonogenesis

Oliver‐Petit¹,

Edouard

Jacques

et al. 2021

Front. Endocrinol.

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ContextCongenital hypothyroidism (CH) is related to dyshormonogenesis in 15% to 40% of the world population and associated with homozygous or heterozygous variants in the main genes of the hormone synthesis pathway. Emerging diagnostic tools, such as next-generation sequencing (NGS), have been used to efficiently explore panels of genes and identify complex mechanisms of pathogenesis.ObjectiveWe explored 19 candidate genes known to be causative for permanent or transient CH to evaluate the role of complex gene variations in CH phenotype.Patients, Design and SettingUsing the NGS approach, we studied 65 newborns with thyroid dyshormonogenesis (TDH). New variants were assessed in silico for pathogenicity.ResultsAmong the 65 infants, 56.9% presented a variant in one or more genes of the thyroid hormone synthesis axis. We identified homozygous or compound heterozygous variants in the TG, DUOX2, TPO, or SLC5A5 genes in 10 infants and heterozygous variants in DUOX2, TG, TPO, and TSHR in 19 others. In seven cases, a heterozygous variant in the TG gene was the unique anomaly detected, but related to disturbed hormonal balance. Oligogenic variants were found in eight infants associated with severe CH and goiter in five of them.ConclusionThe systematic exploration of genes involved in thyroid hormone synthesis by NGS in TDH showed high diagnostic relevance. Oligogenic inheritance could be related to phenotypic heterogeneity and a high frequency of goiter.

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Section: Discussionsupporting

confidence: 65%

Next-Generation Sequencing Analysis Reveals Frequent Familial Origin and Oligogenism in Congenital Hypothyroidism With Dyshormonogenesis

Oliver‐Petit¹,

Edouard

Jacques

et al. 2021

Front. Endocrinol.

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“…Congenital hypothyroidism can be divided into two major types according to its pathogenesis. 80%-85% of CH is caused by defective thyroid glands, such as athyreosis, hypoplastic or ectopic gland [4] ,which is closely related to the gene encoding thyroid transcription factor, such as TSHR [5] , TTF1 [6] ,PAX8 [7] ,NKX2.1 [8] and FOXE1 [9] and so on. 15%-20% of CH patients with thyroid dyshormonogenesis combined with thyroid goiter [1] is inherited as an autosomal recessive trait [10] .…”

Section: Introductionmentioning

confidence: 99%

Study on DEHAL1 Mutations in Patients with Congenital Hypothyroidism and Thyroid Goiter

Han¹,

Zang²,

Zang³

et al. 2016

ijSciences

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Abstract:The objective of this research is to study the types and characteristics of DEHAL1 gene mutation in patients with congenital hypothyroidism (CH) and thyroid goiter from Shandong Province, which can provide some evidence for gene diagnosis of CH. 47 cases of patients who were diagnosed as CH combined with thyroid goiter by neonatal screening and 100 normal controls were selected as subjects and their genome DNA were extracted. All the exons were amplified by polymerase chain reaction (PCR) and PCR products were sequenced by direct sequencing (Sanger sequencing). DNA sequencing results were compared to the DEHAL1 gene reference sequence to see whether there was mutation, and χ2 test was used on the gene frequency of discovered Single Nucleotide Polymorphisms (SNP). The results showed that no DEHAL1 gene mutation was found in 60 cases of CH with thyroid goiter patients and 100 normal controls, however, two SNPs were found(rs672766, IVS3+129C>T; rs2076292, IVS3+142C>T) in intron region. There was no significant difference between the SNP rate in CH patients and normal controls (P > 0.05). It can be concluded that DEHAL1 gene mutation rate is very low which may not be the main factor leading to the congenital hypothyroidism (CH) with thyroid goiter in Shandong Province, China.

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Importance of molecular genetic analysis in the diagnosis and classification of congenital hypothyroidism

Cited by 2 publications

References 10 publications

Next-Generation Sequencing Analysis Reveals Frequent Familial Origin and Oligogenism in Congenital Hypothyroidism With Dyshormonogenesis

Next-Generation Sequencing Analysis Reveals Frequent Familial Origin and Oligogenism in Congenital Hypothyroidism With Dyshormonogenesis

Study on DEHAL1 Mutations in Patients with Congenital Hypothyroidism and Thyroid Goiter

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