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...
Saved in:
| Main Authors: | , , , , , , , |
|---|---|
| Format: | Book |
| Published: |
MDPI AG,
2021-05-01T00:00:00Z.
|
| Subjects: | |
| Online Access: | Connect to this object online. |
| Tags: |
Add Tag
No Tags, Be the first to tag this record!
|
| Summary: | 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. |
|---|---|
| Item Description: | 10.3390/children8060457 2227-9067 |