ESPE Abstracts (2019) 92 RFC9.1

ESPE2019 Rapid Free Communications Fetal, Neonatal Endocrinology and Metabolism (to include Hypoglycaemia) (6 abstracts)

Targeted Next-Generation Sequencing for Congenital Hypothyroidism with Positive Neonatal TSH Screening Results

Takeshi Yamaguchi


University of Hokkaido, Sapporo, Japan. Jichi Children's Medical Center, Shimotsuke, Japan

Background and Objective: Congenital hypothyroidism (CH) is mostly detected with neonatal newborn screening (NBS). CH is the most common neonatal endocrine disorder with an incidence of 1:2,000-1:4,000. However the molecular etiology is sill poorly understood, considering pathogenic variations in candidate genes have been found only in 10-20 % of CH. We performed mutations screening of causative genes through a systematic Next Generation Sequencing (NGS) analysis in CH cases with positive NBS results.

Methods: We performed the genetic analysis of causative 59 genes using NGS in 168 CH cases (53 dyshormonogenesis, 32 dysgenesis, 83 not evaluated). Pathogenicity of novel mutations was assessed in silico.

Results: We identified 12.5 % (21/168) and 5.4 % (9/168) with seemingly monogenic defects and oligogenic defects, respectively. Monogenic defects (21 cases) involved DUOX2 (12), TSHR (5), TG (2), and PAX8 (2). Oligogenic defects (9 cases) had two mutations in two different genes among DUOX2, TG, TSHR, SLC16A2, GLIS3, TPO, SECISBP2, DUOXA1, and SLC26A4.

Discussion: This study identified 12.5 % of monogenic defects in NBS-positive CH, which is similar result as previously reported. In addition, we found 5.4 % in CH patients having oligogenic defects. The role of oligogenicity in etiology of CH remains unclear, however frequent occurrence of several mutations in two or more candidate genes suggest the contribution of oligogenic variants. The systematic NGS analysis is useful in determining an underlying moleculer etiology of CH.

Volume 92

58th Annual ESPE

Vienna, Austria
19 Sep 2019 - 21 Sep 2019

European Society for Paediatric Endocrinology 

Browse other volumes

Article tools

My recent searches

No recent searches.