The c.63A&gt;G polymorphism in the NKX2.5 gene is associated with thyroid hypoplasia in children with thyroid dysgenesis

Cerqueira, Taíse Lima de Oliveira; Ramos, Yanne Rocha; Strappa, Giorgia; Martin, Daniel; Jesus, Mariana; Gonzaga, Jailciele; Ferreira, Paulo H.; Costa, André Leonardo de Castro; Fernandes, Vladimir; Amorim, Tatiana; Ladeia, Ana Marice; Ramos, Helton Estrela

doi:10.1590/2359-3997000000100

Cited by 5 publications

(5 citation statements)

References 21 publications

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“…NKX2-5, also associated with cardiac malformations, was found with 3 heterozygote mutations in a single study with a cohort of 241 patients (32). In our study, seven patients (2 females and 5 males) presented congenital heart disease (CHD) associated with TD, previously described in electronic records (25).…”

Section: Genetics Findingsmentioning

confidence: 52%

“…Along with a greater gender discrepancy, those with ectopy (p ≤ 0.05) and agenesis (p ≤ 0.001) had medians of TSH that were notably higher at the initial newborn screening and confirmatory serum TSH testing compared with hypoplasia and hemiagenesis. To the best of our knowledge we are the first researchers in Bahia to perform this type of genetic analysis for candidate thyroid embryogenesis genes PAX-8, NKX2-5, TSH-R and HES-1 in confirmed cases of permanent CH and TD (25). It should be noted that we excluded NKX2-1 and FOXE-1 from our analysis, based upon the fact that the phenotype presenting in our cohort showed no signs of Bamforth-Lazarus syndrome or neurological findings (26).…”

Section: Genetics Findingsmentioning

confidence: 99%

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Mutation screening in the genes PAX-8, NKX2-5, TSH-R, HES-1 in cohort of 63 Brazilian children with thyroid dysgenesis

Cerqueira¹,

Ramos²,

Strappa³

et al. 2018

Archives of Endocrinology and Metabolism

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Objective: To evaluate the candidate genes PAX-8, NKX2-5, TSH-R and HES-1 in 63 confirmed cases of thyroid dysgenesis. Subjects and methods: Characterization of patients with congenital hypothyroidism into specific subtypes of thyroid dysgenesis with hormone levels (TT4 and TSH), thyroid ultrasound and scintigraphy. DNA was extracted from peripheral blood leukocytes and the genetic analysis was realized by investigating the presence of mutations in the transcription factor genes involved in thyroid development. Results: No mutations were detected in any of the candidate genes. In situ thyroid gland represented 71.1% of all cases of permanent primary congenital hypothyroidism, followed by hypoplasia (9.6%), ectopia (7.8%), hemiagenesis (6.0%) and agenesis (5.5%). The highest neonatal screening TSH levels were in the agenesis group (p < 0.001). Conclusions: Thyroid dysgenesis is possibly a polygenic disorder and epigenetic factors could to be implicated in these pathogeneses.

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Section: Genetics Findingsmentioning

confidence: 52%

Section: Genetics Findingsmentioning

confidence: 99%

Mutation screening in the genes PAX-8, NKX2-5, TSH-R, HES-1 in cohort of 63 Brazilian children with thyroid dysgenesis

Cerqueira¹,

Ramos²,

Strappa³

et al. 2018

Archives of Endocrinology and Metabolism

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“…Cerqueira et al studied with thyroid dysgenesis patients and found polymorphism (c.63A>G) among the study population. This variation did not involve an amino acid alteration [16].…”

Section: Discussionmentioning

confidence: 87%

Identification of Mutation in Exon2 of the NKX2.5 Gene in Bangladeshi Pediatric Patients with Congenital Hypothyroidism

Khatun

Chowdhury

Khan

et al. 2020

EJMED

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Context and rationale: Congenital hypothyroidism is a prevalent endocrine disease that may occur due to the alteration in the sequence of nucleotides of the NKX2.5 gene. Though congenital hypothyroidism is quite common among the Bangladeshi pediatric population, there are few studies on the genetic basis of this disease. Objective: This study aimed to identify any mutation in the exon2 of the NKX2.5 gene in Bangladeshi pediatric patients with congenital hypothyroidism. Methods: Forty (40) Bangladeshi pediatric patients with congenital hypothyroidism were recruited, the sociodemographic data were collected and analyzed, DNA was isolated, quantity and quality of DNA were checked, polymerase chain reaction (PCR) was done, the amplicons were visually validated by gel electrophoresis and cycle sequencing was done by Sanger sequencing. The raw chromatogram data were analyzed and compared with the NCBI database by BLAST (Basic Local Alignment Search Tool) search. Results: Sanger sequencing revealed two types of alteration in the nucleotide sequence. Nine patients showed substitutions (c.1051G>T) and eight patients showed deletions (c.1143 delT-), and both substitution and deletion were present in four patients. This substitution and deletion occurred in the Sequence Tagged Site (STS) of the exon2 of the NKX2.5 gene and these are new variants and not reported in NCBI database. Conclusion: In the present study, two types of variants were identified. So, further study to find out mutational status among Bangladeshi children might be helpful in enriching the database of mutational spectra of pediatric patients with congenital hypothyroidism.

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“…Cerqueira et al demonstrated a significant association of c.63A>G polymorphism with thyroid hypoplasia ( p < 0.036). The c.541G>A variant was observed in only one patient with isolated thyroid hypoplasia [ 11 ]. Long et al through targeted next-generation sequencing of thirteen causative genes in 106 Chinese patients with CH was able to detect one novel missense NKX2-5 mutation (c.416G>A in exon 2, NM_001166176) in one patient with TD (type not specified) [ 12 ].…”

Section: Discussionmentioning

confidence: 99%

NKX2-5 Variant in Two Siblings with Thyroid Hemiagenesis

Szczepanek‐Parulska

Budny

Borowczyk

et al. 2022

IJMS

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Thyroid hemiagenesis (THA) is an inborn absence of one thyroid lobe of largely unknown etiopathogenesis. The aim of the study was to reveal genetic factors responsible for thyroid maldevelopment in two siblings with THA. None of the family members presented with congenital heart defect. The samples were subjected to whole-exome sequencing (WES) (Illumina, TruSeq Exome Enrichment Kit, San Diego, CA 92121 USA). An ultra-rare variant c.839C>T (p.Pro280Leu) in NKX2-5 gene (NM_004387.4) was identified in both affected children and an unaffected father. In the mother, the variant was not present. This variant is reported in population databases with 0.0000655 MAF (GnomAD v3, dbSNP rs761596254). The affected amino acid position is moderately conserved (positive scores in PhyloP: 1.364 and phastCons: 0.398). Functional prediction algorithms showed deleterious impact (dbNSFP v4.1, FATHMM, SIFT) or benign (CADD, PolyPhen-2, Mutation Assessor). According to ACMG criteria, variant is classified as having uncertain clinical significance. For the first time, NKX2-5 gene variants were found in two siblings with THA, providing evidence for its potential contribution to the pathogenesis of this type of thyroid dysgenesis. The presence of the variant in an unaffected parent, carrier of p.Pro280Leu variant, suggests potential contribution of yet unidentified additional factors determining the final penetrance and expression.

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The c.63A>G polymorphism in the NKX2.5 gene is associated with thyroid hypoplasia in children with thyroid dysgenesis

Cited by 5 publications

References 21 publications

Mutation screening in the genes PAX-8, NKX2-5, TSH-R, HES-1 in cohort of 63 Brazilian children with thyroid dysgenesis

Mutation screening in the genes PAX-8, NKX2-5, TSH-R, HES-1 in cohort of 63 Brazilian children with thyroid dysgenesis

Identification of Mutation in Exon2 of the NKX2.5 Gene in Bangladeshi Pediatric Patients with Congenital Hypothyroidism

NKX2-5 Variant in Two Siblings with Thyroid Hemiagenesis

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