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NKX2-5 Variant in Two Siblings with Thyroid Hemiagenesis

1
Department of Endocrinology, Metabolism and Internal Diseases, Poznan University of Medical Sciences, 61-701 Poznan, Poland
2
Department of Medical Simulation, Poznan University of Medical Sciences, 61-701 Poznan, Poland
3
Polish Academy of Sciences, Institute of Biochemistry and Biophysics, 02-106 Warsaw, Poland
4
NanoBioMedical Centre, Adam Mickiewicz University, 61-614 Poznan, Poland
5
MNM Diagnostics Sp. z o.o, 61-695 Poznan, Poland
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Department of Intensive Cardiological Care and Internal Medicine, Poznan University of Medical Sciences, 61-701 Poznan, Poland
7
Department of Pediatric Endocrinology and Rheumatology, Institute of Pediatrics, Poznan University of Medical Sciences, 61-701 Poznan, Poland
*
Author to whom correspondence should be addressed.
These authors contributed equally to this work.
Academic Editor: Maurizio Delvecchio
Int. J. Mol. Sci. 2022, 23(6), 3414; https://doi.org/10.3390/ijms23063414
Received: 21 February 2022 / Revised: 18 March 2022 / Accepted: 19 March 2022 / Published: 21 March 2022
(This article belongs to the Special Issue Molecular Mechanism of Hypothyroidism)
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. View Full-Text
Keywords: thyroid hemiagenesis; thyroid dysgenesis; thyroid transcription factor; NKX2-5 gene; whole-exome sequencing thyroid hemiagenesis; thyroid dysgenesis; thyroid transcription factor; NKX2-5 gene; whole-exome sequencing
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MDPI and ACS Style

Szczepanek-Parulska, E.; Budny, B.; Borowczyk, M.; Zhukov, I.; Szutkowski, K.; Zawadzka, K.; Tahir, R.; Minczykowski, A.; Niedziela, M.; Ruchała, M. NKX2-5 Variant in Two Siblings with Thyroid Hemiagenesis. Int. J. Mol. Sci. 2022, 23, 3414. https://doi.org/10.3390/ijms23063414

AMA Style

Szczepanek-Parulska E, Budny B, Borowczyk M, Zhukov I, Szutkowski K, Zawadzka K, Tahir R, Minczykowski A, Niedziela M, Ruchała M. NKX2-5 Variant in Two Siblings with Thyroid Hemiagenesis. International Journal of Molecular Sciences. 2022; 23(6):3414. https://doi.org/10.3390/ijms23063414

Chicago/Turabian Style

Szczepanek-Parulska, Ewelina, Bartłomiej Budny, Martyna Borowczyk, Igor Zhukov, Kosma Szutkowski, Katarzyna Zawadzka, Raiha Tahir, Andrzej Minczykowski, Marek Niedziela, and Marek Ruchała. 2022. "NKX2-5 Variant in Two Siblings with Thyroid Hemiagenesis" International Journal of Molecular Sciences 23, no. 6: 3414. https://doi.org/10.3390/ijms23063414

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