title: Genotype-phenotype correlations of dyshormonogenetic goiter in children and adolescents from South India.
abstract: BACKGROUND
  Dyshormonogenetic goiter is one of the most common causes of hypothyroidism in children and adolescents in iodine nonendemic areas. The exact genotype-phenotypic correlations (GPCs) and risk categorization of hypothyroid phenotypes of dyshormonogenetic mutations are largely speculative. The genetic studies in pediatric dyshormonogenesis are very sparse from Indian sub-continent. In this context, we analyzed the implications of TPO,NIS, andDUOX2gene mutations in hypothyroid children with dyshormonogenetic hypothyroidism (DH) from South India.
  
  
  METHODS
  This is interdisciplinary prospective study, we employed eight sets of primers and screened for 142 known single nucleotide polymorphisms inTPO,NIS, andDUOX2genes. The subjects were children and adolescents with hypothyroidism due to dyshormonogenetic goiter. Congenital hypothyroidism, iodine deficiency, and Hashimoto's thyroiditis cases were excluded.
  
  
  RESULTS
  We detected nine mutations in 8/22 (36%) children. All the mutations were observed in the intronic regions ofNISgene and none inTPOorDUOX2genes. Except for bi-allelic, synonymous polymorphism ofTPOgene in child number 14, all other mutations were heterozygous in nature. GPCs show that our mutations significantly expressed the phenotypic traits such as overt hypothyroidism, goiter, and existence of family history. Other phenotypic characters such as sex predilection, the age of onset and transitory nature of hypothyroidism were not significantly affected by these mutations.
  
  
  CONCLUSIONS
  NISgene mutations alone appears to be most prevalent mutations in DH among South Indian children and these mutations significantly influenced phenotypic expressions such as severity of hypothyroidism, goiter rates, and familial clustering.
authors.affiliation: Department of Biochemistry, MediCiti Institute of Medical Sciences, Hyderabad, Telangana, India.
authors.forename: Bangaraiah Gari
authors.initials: BG
authors.lastname: Ramesh
authors.affiliation: Department of Endocrine Surgery, Endocare Hospital, Vijayawada, Andhra Pradesh, India.
authors.forename: Panchangam Ramakanth
authors.initials: PR
authors.lastname: Bhargav
authors.affiliation: Department of Anatomy, MediCiti Institute of Medical Sciences, Hyderabad, Telangana, India.
authors.forename: Bangaraiah Gari
authors.initials: BG
authors.lastname: Rajesh
authors.affiliation: Department of Endocrine Surgery, Endocare Hospital, Vijayawada, Andhra Pradesh, India.
authors.forename: Nangedda Vimala
authors.initials: NV
authors.lastname: Devi
authors.affiliation: Department of Research and Development, Saveetha University, Chennai, Tamil Nadu, India.
authors.forename: Rajagopalan
authors.initials: R
authors.lastname: Vijayaraghavan
authors.affiliation: Department of Biochemistry, MediCiti Institute of Medical Sciences, Hyderabad, Telangana, India.
authors.forename: Bhongir Aparna
authors.initials: BA
authors.lastname: Varma
keywords: DUOX gene; NIS gene; TPO gene; dyshormonogenetic goiter; hypothyroidism