One Base Deletion (c.2422delT) in the TPO Gene Causes Severe Congenital Hypothyroidism
Hakan Cangül1, Murat Doğan2, Yaman Sağlam3, Michaela Kendall4, Kristien Boelaert5, Timothy G Barrett5, Eamonn R Maher61Bahçeşehir University Faculty Of Medicine, Department Of Medical Genetics, İstanbul, Turkey2Yüzüncü Yıl University, Faculty Of Medicine, Division Of Pediatric Endocrinology, Van, Turkey
3Medical Park Göztepe Hospital, Centre For Genetic Diagnosis, İstanbul, Turkey
4Southampton Faculty Department Of Child Health, Division Of Clinical And Experimental Sciences, Uk
5University Of Birmingham, School Of Clinical And Experimental Medicine, Centre For Rare Diseases And Personalised Medicine, Birmingham, Uk
6Cambridge University Of Clinical Faculty, Academic Department Of Medical Genetics, Cambridge, Uk
Objective: Congenital hypothyroidism (CH) is the most common neonatal endocrine disorder and mutations in the TPO gene have been reported to cause CH. Our aim in this study was to determine the genetic basis of CH in two affected individuals coming from a consanguineous family.
Methods: Since CH is usually inherited in autosomal recessive manner in consanguineous/multi-case 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 Sanger sequencing.
Results: The family showed potential linkage to the TPO gene and we detected a deletion (c.2422delT) in both cases. The mutation segregated with disease status in the family.
Conclusion: This study demonstrates that a single base deletion in the carboxyl-terminal coding region of the TPO gene could cause CH and helps to establish a genotype/phenotype correlation associated with the mutation. The study also highlights the importance of molecular genetic studies in the definitive diagnosis and accurate classification of CH.
Manuscript Language: English
