ESPE2023 Poster Category 1 Thyroid (44 abstracts)
Clinical and molecular characteristics of 147 patients with primary congenital hypothyroidism: A single-center experience
Zehra Yavaş Abalı 1 , Ceren Alavanda 2 , Mehmet Eltan 3,4 , Esra Arslan Ateş 5 , Didem Helvacioglu 1 , Busra Gurpinar Tosun 1 , Ahmet Kahveci 3 , İlknur Kurt 3 , Elif Keleştemur 3 , Tulay Guran 3 , Abdullah Bereket 3 & Serap Turan 3
1Pediatric Endocrinology Unit, Marmara University Pendik Research and Training Hospital, Istanbul, Turkey. 2Department of Medical Genetics, Marmara University, School of Medicine, Istanbul, Turkey. 3Department of Pediatric Endocrinology and Diabetes, Marmara University School of Medicine, Istanbul, Turkey. 4Pediatric Endocrinology Unit, Sancaktepe Şehit Prof Dr İlhan Varank Research and Training Hospital, Istanbul, Turkey. 5Department of Medical Genetics, Marmara University Pendik Research and Training Hospital, Istanbul, Turkey
Background: Next-generation sequencing (NGS) technologies have improved our knowledge about the genetic basis of congenital hypothyroidism (CH). The objective of our study was to evaluate the molecular genetic etiology in our primary CH cohort by using the NGS-based panel.
Subjects and Methods: The clinical and genetic characteristics of 147 patients (61 female) from 129 unrelated families were evaluated. The patients were categorized as thyroid dysgenesis (TD) and gland in situ (GIS) according to the thyroid ultrasonography and/or thyroid scintigraphy. Clinical Exome Sequencing (CES) was performed using SOPHIA Clinical Exome Solution V2 (Boston, USA) via the Illumina Nextseq 550 platform (San Diego, CA, USA). The Human Gene Mutation Database (HGMD) and ClinVar databases were used to determine whether the detected variants were novel or previously reported. Segregation analysis was performed in selected cases and families.
Results: The median age at admission was 24 days (IQR 14-41 days). The mean for gestational age was 38.4±2.2 weeks. Birth weight was SDS 0.1±1.1, and the SGA ratio was 3.6%. The rate of consanguinity was 30.8%. The hospitalization rate in the neonatal care unit was 27.6%, and neonatal jaundice was reported at 58.1%. The median values of TSH and free T4 at admission were 79.0 mU/L (IQR 21-321) and 8.1 pmol/L (IQR 3.8-12.5), respectively. TD ratio was 27.7% (55.2% ectopy, 24.1% hypoplasia, 13.8% agenesis, 6.9% hemiagenesis) and 72.3% GIS. Clinically relevant pathogenic variants were identified in 32.7% (9.1% in TD, 44.2% in GIS, P<0.001) of the cohort. Pathogenic/likely pathogenic variants were detected in TSHR (n=13), TPO (13 cases from 6 families), and DUOX2 (8 biallelic, 3 monoallelic) followed by PAX8 (4 cases from two families), TG (n=2), NKX2-1 (n=1), SLC5A5 (n=1), SLC26A4 (n=1), DUOXA2 (n=1), ELN (n=1).
Conclusion: Clinically relevant pathogenic variants were detected in approximately 1/3 of the cases in our congenital hypothyroidism cohort. The molecular etiology was identified more frequently in cases with GIS compared to dysgenesis.
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