title: Novel TSHbeta subunit gene mutation causing congenital central hypothyroidism in a newborn male.
abstract: Newborn screening programs that use only high TSH levels as a marker for hypothyroidism may overlook neonates with congenital hypothyroidism (CH) due to TSH deficiency. We sought the cause of TSH deficiency in a neonate with low levels of thyroxine and TSH. The coding region of the TSHbeta gene was amplified and its sequence examined for mutations. Two mutations in exon 3 were identified: 1) a nucleotide deletion of T410 in codon 105 resulting in a frameshift in one allele, and 2) a previously unreported nucleotide deletion of T266 in codon 57, causing a frameshift and a premature stop at codon 62 in the other allele. We describe a compound heterozygous patient with TSHbeta mutations at codons 57 and 105 that interfered with a critical disulfide bond in the TSH molecule and caused CH. State screening programs that measure both T4 and TSH levels have the potential to detect newborns with congenital central hypothyroidism.
authors.affiliation: Division of Pediatric Endocrinology, University of Florida, Gainesville, FL 32610, USA. moralae@peds.ufl.edu
authors.forename: Alba E
authors.initials: AE
authors.lastname: Morales
authors.forename: Jing Da
authors.initials: JD
authors.lastname: Shi
authors.forename: Cong Yi
authors.initials: CY
authors.lastname: Wang
authors.forename: Jin-Xiong
authors.initials: JX
authors.lastname: She
authors.forename: Andrew
authors.initials: A
authors.lastname: Muir
mesh_terms: D003409:Congenital Hypothyroidism; D005307:Fertilization in Vitro; D006579:Heterozygote; D020249:Hormone Replacement Therapy; D006801:Humans; D007037:Hypothyroidism / Q000188:drug therapy / Q000235:genetics*; D007231:Infant, Newborn; D007262:Infusions, Intravenous; D008297:Male; D009154:Mutation; D017422:Sequence Analysis, DNA; D037322:Thyrotropin, beta Subunit / Q000097:blood / Q000172:deficiency* / Q000235:genetics*; D013973:Thyrotropin-Releasing Hormone / Q000494:pharmacology / Q000627:therapeutic use; D013974:Thyroxine / Q000097:blood / Q000627:therapeutic use; D013997:Time Factors; D016896:Treatment Outcome
chemical_list: D037322:Thyrotropin, beta Subunit; D013973:Thyrotropin-Releasing Hormone; D013974:Thyroxine