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.