title: Two novel TSHR gene mutations (p.R528C and c.392+4del4) associated with congenital hypothyroidism.
abstract: Inactivating mutations of the thyrotropin receptor (TSHR) gene are responsible for non-goitrogenic congenital hypothyroidism (CHNG). This study aimed to investigate mutations in the TSHR gene in 20 children with CHNG. Genomic DNA was extracted from peripheral blood leukocytes and was used for mutation screening by direct sequencing. Analyses of the TSHR gene revealed two novel variants in a 2-year-old boy with thyroid hypoplasia: a missense mutation c.1582C>T (p.R528C) and a splice-site deletion c.392+4del4. Bioinformatics analysis demonstrated that both variants are capable of causing disease. Family members of the patient with two mutations and normal controls were also recruited and investigated. Germline mutations from the proband's family were consistent with an autosomal recessive inheritance pattern. These findings indicate that two novel inactivating mutations (p.R528C and c.392+4del4) in the TSHR gene can cause CHNG.
authors: a Department of Neonatal Screening and Care , Women and Children's Hospital of Suqian , Suqian , China.
authors: Ya-Li
authors: YL
authors: Qiu
authors: b Department of Endocrinology and Metabolism , Huai'an Hospital Affiliated to Xuzhou Medical College and Huai'an Second People's Hospital , Huai'an , China.
authors: Shao-Gang
authors: SG
authors: Ma
authors: b Department of Endocrinology and Metabolism , Huai'an Hospital Affiliated to Xuzhou Medical College and Huai'an Second People's Hospital , Huai'an , China.
authors: Hong
authors: H
authors: Liu
authors: c Department of Children Healthcare , Women and Children's Hospital of Huai'an , Huai'an Jiangsu , China.
authors: Hong-Ni
authors: HN
authors: Yue
mesh_terms: D002648:Child; D002675:Child, Preschool; D003409:Congenital Hypothyroidism / Q000235:genetics*; D005260:Female; D006801:Humans; D008297:Male; D009154:Mutation; D011989:Receptors, Thyrotropin / Q000235:genetics*
chemical_list: D011989:Receptors, Thyrotropin
keywords: Congenital hypothyroidism; TSHR gene; mutation