Functional characterization of four novel PAX8 mutations causing congenital hypothyroidism: new evidence for haploinsufficiency as a disease mechanism

• Published in: European journal of endocrinology Vol. 167; no. 5; pp. 625 - 632
• Main Authors: Narumi, Satoshi, Araki, Shunsuke, Hori, Naoaki, Muroya, Koji, Yamamoto, Yukiyo, Asakura, Yumi, Adachi, Masanori, Hasegawa, Tomonobu
• Format: Journal Article
• Language: English
• Published: Bristol BioScientifica 01.11.2012
• Subjects: Adult; Biological and medical sciences; Blotting, Western; Cell Culture Techniques; Child; Child, Preschool; Clinical Study; Congenital Hypothyroidism - diagnostic imaging; Congenital Hypothyroidism - genetics; Electrophoretic Mobility Shift Assay; Endocrinopathies; Female; Frameshift Mutation; Fundamental and applied biological sciences. Psychology; Haploinsufficiency; Humans; Infant; Male; Medical sciences; Mutation; Mutation, Missense; Non tumoral diseases. Target tissue resistance. Benign neoplasms; Paired Box Transcription Factors - genetics; PAX8 Transcription Factor; Plasmids; Thyroid Dysgenesis - genetics; Thyroid Gland - cytology; Thyroid Gland - diagnostic imaging; Thyroid Gland - metabolism; Thyroid. Thyroid axis (diseases); Transcriptional Activation; Transfection; Ultrasonography; Vertebrates: endocrinology; Endocrinopathy; Characterization; Endocrine gland; Congenital; Thyroid diseases; Thyroid gland; Mutation; Hypothyroidism; Congenital disease; Endocrinology; Mechanism

Background Individuals carrying a heterozygous inactivating PAX8 mutation are affected by congenital hypothyroidism (CH), although heterozygous Pax8 knockout mice are not. It has remained unclear whether CH in PAX8 mutation carriers is caused by haploinsufficiency or a dominant negative mechanism. O...