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Document Version Version Comment Date Status
535979.0 [No comment] 01.03.2011 15:17 Released

ID: 535979.0, MPI für molekulare Genetik / Department of Human Molecular Genetics
Screening chromosomal aberrations by array comparative genomic hybridization in 80 patients with congenital hypothyroidism and thyroid dysgenesis.
Authors:Thorwarth, A.; Mueller, I.; Biebermann, H.; Ropers, Hans-Hilger; Grueters, A.; Krude, H.; Ullmann, Reinhard
Date of Publication (YYYY-MM-DD):2010-07-01
Title of Journal:The Journal of Clinical Endocrinology & Metabolism
Journal Abbrev.:J. Clin. Endocrinol. Metab.
Issue / Number:7
Start Page:3446
End Page:3452
Copyright:© 2010 by The Endocrine Society
Review Status:not specified
Audience:Experts Only
Abstract / Description:Objective:
Congenital hypothyroidism occurs in 1:3500 live births and is therefore the most common congenital endocrine disorder. A spectrum of defective thyroid morphology, termed thyroid dysgenesis (TD), represents 80% of permanent congenital hypothyroidism cases. Although several candidate genes have been implicated in thyroid development, comprehensive screens failed to detect mutation carriers in a significant number of patients with nonsyndromic TD. Due to the sporadic occurrence of TD, de novo chromosomal rearrangements are conceivably representing one of the molecular mechanisms participating in its etiology.
The introduction of array comparative genomic hybridization (CGH) has provided the ability to map DNA copy number variations (CNVs) genome wide with high resolution. We performed an array CGH screen of 80 TD patients to determine the role of CNVs in the etiology of the disease.
We identified novel CNVs that have not been described as frequent variations in the healthy population in 8.75% of all patients. These CNVs exclusively affected patients with athyreosis or thyroid hypoplasia and were nonrecurrent, and the regions flanking the CNVs were not enriched for segmental duplications.
The high rate of chromosomal changes in TD argues for an involvement of CNVs in the etiology of this disease. Yet the lack of recurrent aberrations suggests that the genetic causes of TD are heterogenous and not restricted to specific genomic hot spots. Thus, future studies may have to shift the focus from singling out specific genes to the identification of deregulated pathways as the underlying cause of the disease.
Comment of the Author/Creator:Address all correspondence and requests for reprints to: Prof. Dr. H. Krude, M.D. (patient cohort), Charité University Medicine Berlin, Institute for Experimental Pediatric Endocrinology, Augustenburger Platz 1, 13353 Berlin, Germany. E-mail: Or Dr. R. Ullmann (array CGH), Max Planck Institute for Molecular Genetics, Ihnestrasse 63-73, 14195 Berlin, Germany. E-mail:
External Publication Status:published
Document Type:Article
Communicated by:Hans-Hilger Ropers
Affiliations:MPI für molekulare Genetik
External Affiliations:1.Institute for Experimental Pediatric Endocrinology (A.T., H.B., A.G., H.K.), Charite University Medicine, 13353 Berlin, Germany.