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| Familial congenital hypothyroidism due to inactivating mutation of the thyrotropin receptor causing profound hypoplasia of the thyroid gland |
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| Author(s): Abramowicz MJ, Duprez L, Parma J, Vassart G, Heinrichs C |
| Source: JOURNAL OF CLINICAL INVESTIGATION Volume: 99 Issue: 12 Pages: 3018-3024 Published: JUN 15 1997 |
| Times Cited: 124 References: 35 |
| Abstract: Thyroid gland agenesis is the most common cause of congenital hypothyroidism and is usually sporadic. We investigated a brother and sister from consanguineous parents, ascertained through systematic newborn screening, and initially diagnosed with thyroid agenesis. Careful cervical ultrasonography in both patients revealed a very hypoplastic thyroid gland. By direct sequencing of the thyrotropin receptor gene, we identified the substitution of threonine in place of a highly conserved alanine at position 553, in the fourth predicted transmembrane domain. The mutation was found homozygous in the affected siblings, and heterozygous in both parents and two unaffected siblings. Functional analysis in transfected COS-7 cells showed that it resulted in extremely low expression at the cell surface as compared with the wild-type receptor, in spite of an apparently normal intracellular synthesis. The small amount of mutated receptor expressed at the surface of transfected cells bound thyrotropin with normal affinity and responded in terms of cAMP production, but the in vivo significance of these data from overexpressed receptor in transfected cells is unclear. Of note, blood thyroglobulin was unexpectedly elevated in the patients at the time of diagnosis, a finding that might prove useful in refining etiologies of congenital hypothyroidism. |
| Document Type: Article |
| Language: English |
| Reprint Address: Abramowicz, MJ (reprint author), ERASME UNIV HOSP, SERV GENET, 808 ROUTE LENNIK, B-1070 BRUSSELS, BELGIUM |
Addresses:
1. HOP UNIV ENFANTS REINE FABIOLA, DEPT PEDIAT, B-1020 BRUSSELS, BELGIUM
2. FREE UNIV BRUSSELS, INST RECH INTERDISCIPLINAIRE BIOL HUMAINE & NUCL, B-1070 BRUSSELS, BELGIUM |
| Publisher: ROCKEFELLER UNIV PRESS, 1114 FIRST AVE, 4TH FL, NEW YORK, NY 10021 |
| Subject Category: Medicine, Research & Experimental |
| IDS Number: XH277 |
| ISSN: 0021-9738 |
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