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J Pediatr Genet 2015; 04(04): 194-198
DOI: 10.1055/s-0035-1565268
Original Article
Georg Thieme Verlag KG Stuttgart · New York

A Homozygous TPO Gene Duplication (c.1184_1187dup4) Causes Congenital Hypothyroidism in Three Siblings Born to a Consanguineous Family

Hakan Cangul
1   Department of Medical Genetics, Istanbul Medipol University, International School of Medicine, Istanbul, Turkey
2   Centre for Rare Diseases and Personalised Medicine, University of Birmingham, School of Clinical and Experimental Medicine, Birmingham, United Kingdom
,
Banu K. Aydin
3   Pediatric Endocrinology Unit, Istanbul Faculty of Medicine, Istanbul University, Turkey
,
Firdevs Bas
3   Pediatric Endocrinology Unit, Istanbul Faculty of Medicine, Istanbul University, Turkey
› Institutsangaben
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Publikationsverlauf

18. März 2015

16. April 2015

Publikationsdatum:
14. Oktober 2015 (online)

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Abstract

Congenital hypothyroidism (CH) is the most common neonatal endocrine disease, and germ-line mutations in the TPO gene cause the inherited form of the disease. Our aim in this study was to determine the genetic basis of congenital hypothyroidism in three affected children coming from a consanguineous Turkish family. Because CH is usually inherited in autosomal recessive manner in consanguineous/multicase families, we adopted a two-stage strategy of genetic linkage studies and targeted sequencing of the candidate genes. First, we investigated the potential genetic linkage of the family to any known CH locus, using microsatellite markers, and then screened for mutations in linked-gene by conventional sequencing. The family showed potential linkage to the TPO gene and we detected a homozygous duplication (c.1184_1187dup4) in all cases. The mutation segregated with disease status in the family. This study confirms the pathogenicity of the c.1184_1187dup4 mutation in the TPO gene and helps establish a genotype/phenotype correlation associated with this mutation. It also highlights the importance of molecular genetic studies in the definitive diagnosis and accurate classification of CH.

Keywords

TPO - mutation - genetics - duplication - congenital hypothyroidism - thyroid dyshormonogenesis
 

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