Further Evidence That Defects in Main Thyroid Dysgenesis-Related Genes Are an Uncommon Etiology for Primary Congenital Hypothyroidism in Mexican Patients: Report of Rare Variants in <i>FOXE1</i>, <i>NKX2-5</i> and <i>TSHR</i>
Mexico shows a high birth prevalence of congenital hypothyroidism (CH) due to thyroid dysgenesis (TD). <i>PAX8</i> defects underlie only 1% of these cases and <i>NKX2-1</i> does not seem to be involved. Here, we analyzed other TD-related genes in 128 non-related Mexican patie...
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| Format: | Article |
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MDPI AG
2021-05-01
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| Series: | Children |
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| Online Access: | https://www.mdpi.com/2227-9067/8/6/457 |
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| author | Miguel Angel Alcántara-Ortigoza Iraís Sánchez-Verdiguel Liliana Fernández-Hernández Sergio Enríquez-Flores Aidy González-Núñez Nancy Leticia Hernández-Martínez Carmen Sánchez Ariadna González-del Angel |
| author_facet | Miguel Angel Alcántara-Ortigoza Iraís Sánchez-Verdiguel Liliana Fernández-Hernández Sergio Enríquez-Flores Aidy González-Núñez Nancy Leticia Hernández-Martínez Carmen Sánchez Ariadna González-del Angel |
| author_sort | Miguel Angel Alcántara-Ortigoza |
| collection | DOAJ |
| description | Mexico shows a high birth prevalence of congenital hypothyroidism (CH) due to thyroid dysgenesis (TD). <i>PAX8</i> defects underlie only 1% of these cases and <i>NKX2-1</i> does not seem to be involved. Here, we analyzed other TD-related genes in 128 non-related Mexican patients (females 77.3%; 6 months to 16.6 years) with non-syndromic CH-TD diagnosis established by clinical evaluation, thyroid hormone serum profiling, and scintigraphy (74%) or ultrasonography (26%). We performed Sanger sequencing of <i>FOXE1</i>, <i>NKX2-5</i>, and <i>TSHR</i> and evaluated copy number variations (CNVs) in <i>TSHR</i>, <i>FOXE1</i>, <i>PAX8</i>, and <i>NKX2-1</i> by multiplex ligation-dependent probe amplification. Odds ratios for TD risk were explored for <i>FOXE1</i> polyalanine stretches [polyAla-rs71369530] in cases and controls (N = 116). Five rare missense changes cataloged as benign (<i>NKX2-5</i>:p.(Ala119Ser)-rs137852684), of unknown significance (<i>FOXE1</i>:p.(Ala335Gly)-rs543372757; <i>TSHR</i>:p.(Asp118Asn)-rs1414102266), and likely pathogenic (<i>FOXE1</i>:p.(Gly124Arg)-rs774035532; <i>TSHR</i>:p.(Trp422Arg)-rs746029360) accounted for 1.5% (N = 2/128) of clinically relevant genotypes (supported in part by protein modeling) in CH-TD. No CNVs were identified, nor did polyAla > 14 alanines in <i>FOXE1</i> significantly protect against TD. The present and previously published data collectively show that small clinically relevant germline variants in <i>PAX8</i>, <i>FOXE1,</i> and <i>TSHR</i> are found in only a very small proportion (2.5%) of isolated CH-TD Mexican patients. |
| first_indexed | 2024-03-10T10:52:57Z |
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| id | doaj.art-bc48209bf3ff47c7a0adf37f530cc2d3 |
| institution | Directory Open Access Journal |
| issn | 2227-9067 |
| language | English |
| last_indexed | 2024-03-10T10:52:57Z |
| publishDate | 2021-05-01 |
| publisher | MDPI AG |
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| spelling | doaj.art-bc48209bf3ff47c7a0adf37f530cc2d32023-11-21T22:07:16ZengMDPI AGChildren2227-90672021-05-018645710.3390/children8060457Further Evidence That Defects in Main Thyroid Dysgenesis-Related Genes Are an Uncommon Etiology for Primary Congenital Hypothyroidism in Mexican Patients: Report of Rare Variants in <i>FOXE1</i>, <i>NKX2-5</i> and <i>TSHR</i>Miguel Angel Alcántara-Ortigoza0Iraís Sánchez-Verdiguel1Liliana Fernández-Hernández2Sergio Enríquez-Flores3Aidy González-Núñez4Nancy Leticia Hernández-Martínez5Carmen Sánchez6Ariadna González-del Angel7Laboratorio de Biología Molecular, Subdirección de Investigación Médica, Instituto Nacional de Pediatría, Secretaría de Salud, Ciudad de Mexico CP 04530, MexicoConsulta Externa, Instituto Nacional de Pediatría, Secretaría de Salud, Programa de Maestría y Doctorado en Ciencias Médicas, Odontológicas y de la Salud, UNAM, Ciudad de Mexico CP 04530, MexicoLaboratorio de Biología Molecular, Subdirección de Investigación Médica, Instituto Nacional de Pediatría, Secretaría de Salud, Ciudad de Mexico CP 04530, MexicoGrupo de Investigación en Biomoléculas y Salud Infantil, Laboratorio de Errores Innatos del Metabolismo y Tamiz, Instituto Nacional de Pediatría, Ciudad de Mexico CP 04530, MexicoHospital Regional Materno Infantil de Alta Especialidad de Nuevo León, Guadalupe CP 67140, MexicoLaboratorio de Biología Molecular, Subdirección de Investigación Médica, Instituto Nacional de Pediatría, Secretaría de Salud, Ciudad de Mexico CP 04530, MexicoLaboratorio de Seguimiento del Neurodesarrollo, Instituto Nacional de Pediatría, Ciudad de Mexico CP 04530, MexicoLaboratorio de Biología Molecular, Subdirección de Investigación Médica, Instituto Nacional de Pediatría, Secretaría de Salud, Ciudad de Mexico CP 04530, MexicoMexico shows a high birth prevalence of congenital hypothyroidism (CH) due to thyroid dysgenesis (TD). <i>PAX8</i> defects underlie only 1% of these cases and <i>NKX2-1</i> does not seem to be involved. Here, we analyzed other TD-related genes in 128 non-related Mexican patients (females 77.3%; 6 months to 16.6 years) with non-syndromic CH-TD diagnosis established by clinical evaluation, thyroid hormone serum profiling, and scintigraphy (74%) or ultrasonography (26%). We performed Sanger sequencing of <i>FOXE1</i>, <i>NKX2-5</i>, and <i>TSHR</i> and evaluated copy number variations (CNVs) in <i>TSHR</i>, <i>FOXE1</i>, <i>PAX8</i>, and <i>NKX2-1</i> by multiplex ligation-dependent probe amplification. Odds ratios for TD risk were explored for <i>FOXE1</i> polyalanine stretches [polyAla-rs71369530] in cases and controls (N = 116). Five rare missense changes cataloged as benign (<i>NKX2-5</i>:p.(Ala119Ser)-rs137852684), of unknown significance (<i>FOXE1</i>:p.(Ala335Gly)-rs543372757; <i>TSHR</i>:p.(Asp118Asn)-rs1414102266), and likely pathogenic (<i>FOXE1</i>:p.(Gly124Arg)-rs774035532; <i>TSHR</i>:p.(Trp422Arg)-rs746029360) accounted for 1.5% (N = 2/128) of clinically relevant genotypes (supported in part by protein modeling) in CH-TD. No CNVs were identified, nor did polyAla > 14 alanines in <i>FOXE1</i> significantly protect against TD. The present and previously published data collectively show that small clinically relevant germline variants in <i>PAX8</i>, <i>FOXE1,</i> and <i>TSHR</i> are found in only a very small proportion (2.5%) of isolated CH-TD Mexican patients.https://www.mdpi.com/2227-9067/8/6/457congenital hypothyroidism<i>FOXE1</i>Mexican populationmultiplex ligation-dependent probe amplification (MLPA)<i>NKX2-1</i><i>NKX2-5</i> |
| spellingShingle | Miguel Angel Alcántara-Ortigoza Iraís Sánchez-Verdiguel Liliana Fernández-Hernández Sergio Enríquez-Flores Aidy González-Núñez Nancy Leticia Hernández-Martínez Carmen Sánchez Ariadna González-del Angel Further Evidence That Defects in Main Thyroid Dysgenesis-Related Genes Are an Uncommon Etiology for Primary Congenital Hypothyroidism in Mexican Patients: Report of Rare Variants in <i>FOXE1</i>, <i>NKX2-5</i> and <i>TSHR</i> Children congenital hypothyroidism <i>FOXE1</i> Mexican population multiplex ligation-dependent probe amplification (MLPA) <i>NKX2-1</i> <i>NKX2-5</i> |
| title | Further Evidence That Defects in Main Thyroid Dysgenesis-Related Genes Are an Uncommon Etiology for Primary Congenital Hypothyroidism in Mexican Patients: Report of Rare Variants in <i>FOXE1</i>, <i>NKX2-5</i> and <i>TSHR</i> |
| title_full | Further Evidence That Defects in Main Thyroid Dysgenesis-Related Genes Are an Uncommon Etiology for Primary Congenital Hypothyroidism in Mexican Patients: Report of Rare Variants in <i>FOXE1</i>, <i>NKX2-5</i> and <i>TSHR</i> |
| title_fullStr | Further Evidence That Defects in Main Thyroid Dysgenesis-Related Genes Are an Uncommon Etiology for Primary Congenital Hypothyroidism in Mexican Patients: Report of Rare Variants in <i>FOXE1</i>, <i>NKX2-5</i> and <i>TSHR</i> |
| title_full_unstemmed | Further Evidence That Defects in Main Thyroid Dysgenesis-Related Genes Are an Uncommon Etiology for Primary Congenital Hypothyroidism in Mexican Patients: Report of Rare Variants in <i>FOXE1</i>, <i>NKX2-5</i> and <i>TSHR</i> |
| title_short | Further Evidence That Defects in Main Thyroid Dysgenesis-Related Genes Are an Uncommon Etiology for Primary Congenital Hypothyroidism in Mexican Patients: Report of Rare Variants in <i>FOXE1</i>, <i>NKX2-5</i> and <i>TSHR</i> |
| title_sort | further evidence that defects in main thyroid dysgenesis related genes are an uncommon etiology for primary congenital hypothyroidism in mexican patients report of rare variants in i foxe1 i i nkx2 5 i and i tshr i |
| topic | congenital hypothyroidism <i>FOXE1</i> Mexican population multiplex ligation-dependent probe amplification (MLPA) <i>NKX2-1</i> <i>NKX2-5</i> |
| url | https://www.mdpi.com/2227-9067/8/6/457 |
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