title: Congenital hypothyroidism caused by a novel homozygous mutation in the thyroglobulin gene.
abstract: Congenital hypothyroidism (CH) due to thyroglobulin (TG) deficit is an autosomal recessive disease (OMIM #274700) characterized by hypothyroidism, goiter, low serum TG, and a negative perchlorate discharge test. The aim of this study was to perform the genetic analysis of the TG gene in two sisters born from consanguineus parents and affected by CH and low serum TG levels. The index patient and her sister were identified at neonatal screening for CH and treated with L-thyroxine (L-T4). After discontinuation of L-T4 therapy, hypothyroidism was confirmed, serum TG was undetectable, and no organification defect after (123)I scintigraphy and perchlorate test was shown; thyroid ultrasound showed a eutopic gland of normal size. DNA was extracted from peripheral white blood cells of the two sisters and the father. All 48 exons of TG gene were amplified by polymerase chain reaction and subjected to direct sequencing. A novel homozygous point mutation in exon 10 of TG gene was identified in the patient and her sister. The mutation determined a stop codon at position 768 (R768X) resulting in an early truncated protein or in the complete absence of the protein. The father (euthyroid) was heterozygous carrier of the mutation.
  
  
  CONCLUSIONS
  Genetic analysis of TG gene was performed in two sisters affected by CH. A novel point mutation of the TG gene determining a stop codon at position 768 of the protein was identified. The early truncated nonfunctioning protein or the absence of the protein due to the premature degradation of abnormal mRNA may be responsible of the observed phenotype.
authors: Dipartimento di Medicina Clinica e Sperimentale, Sezione di Endocrinologia, Università di Pisa, Azienda Ospedaliero-Universitaria Pisana, Pisa, Italy.
authors: Patrizia
authors: P
authors: Agretti
authors: Giuseppina
authors: G
authors: De Marco
authors: Caterina
authors: C
authors: Di Cosmo
authors: Eleonora
authors: E
authors: Ferrarini
authors: Lucia
authors: L
authors: Montanelli
authors: Brunella
authors: B
authors: Bagattini
authors: Paolo
authors: P
authors: Vitti
authors: Massimo
authors: M
authors: Tonacchera
mesh_terms: D000293:Adolescent; D000328:Adult; D003409:Congenital Hypothyroidism / Q000235:genetics* / Q000473:pathology; D003241:Consanguinity; D005220:Fathers; D005260:Female; D005784:Gene Amplification; D006801:Humans; D008297:Male; D017354:Point Mutation; D017422:Sequence Analysis, DNA; D035781:Siblings; D013954:Thyroglobulin / Q000235:genetics*; D013960:Thyroid Function Tests
chemical_list: D013954:Thyroglobulin