title: Genetics of specific phenotypes of congenital hypothyroidism: a population-based approach.
abstract: Congenital hypothyroidism (CH) may cause severe and irreversible neurologic and developmental abnormalities when not recognized early. Many millions of newborns have now been screened and many thousands of patients with CH have been identified. Approximately 80%-85% have defects of thyroid gland development, while 15%-20% have congenital errors of thyroid hormone biosynthesis. An entire population screened for CH over a long period of time, was studied in the present report, using a population-based approach. In particular, two CH phenotypes, both presenting with in situ thyroid gland (patients with either goiter or with thyroid gland volume ranging from normal to hypoplasic) were analyzed. Mutations were searched in some of the most likely candidate genes: thyroperoxidase (TPO) in patients with CH goiter, Pax8 and thyrotropin receptor (TSHR) in the other group. In the former group (n = 8), four TPO gene mutations were identified in three patients. One patient was a compound heterozygous. In two cases an already described mutation (1277(insGGCC)) was present; in two other cases mutations not previously described (1996(G-->T) and 2295(G-->A)), which induced aminoacid variations with a Glu --> Stop and Val --> Ile changes, respectively, were identified. In all patients mutations were inherited from one of the parents. In the case of the compound heterozygous patient, one mutation was inherited from the mother (1277(insGGCC)) and the other from the father (1996(G-->T), Glu --> Stop). In the latter group (n = 8), a patient with a 16-base pair C(T)(13)CC deletion in TSHR gene intron 8, 42-bp distal to exon/intron 8 splice junction, was identified. No mutation was identified in Pax8 gene.
authors.affiliation: Istituto di Medicina Interna, Malattie Endocrine e del Metabolismo dell'Università di Catania, Ospedale Garibaldi, Catania, Italy.
authors.forename: Francesca
authors.initials: F
authors.lastname: Calaciura
authors.forename: Giueppe
authors.initials: G
authors.lastname: Miscio
authors.forename: Angelo
authors.initials: A
authors.lastname: Coco
authors.forename: Daniela
authors.initials: D
authors.lastname: Leonardi
authors.forename: Carmela
authors.initials: C
authors.lastname: Cisternino
authors.forename: Concetto
authors.initials: C
authors.lastname: Regalbuto
authors.forename: Maura
authors.initials: M
authors.lastname: Bozzali
authors.forename: Raffaella
authors.initials: R
authors.lastname: Maiorana
authors.forename: Annalisa
authors.initials: A
authors.lastname: Ranieri
authors.forename: Anna
authors.initials: A
authors.lastname: Carta
authors.forename: Massimo
authors.initials: M
authors.lastname: Buscema
authors.forename: Vincenzo
authors.initials: V
authors.lastname: Trischitta
authors.forename: Lidia
authors.initials: L
authors.lastname: Sava
authors.forename: Vittorio
authors.initials: V
authors.lastname: Tassi
mesh_terms: D003409:Congenital Hypothyroidism; D004268:DNA-Binding Proteins / Q000235:genetics; D005820:Genetic Testing; D006042:Goiter / Q000151:congenital / Q000235:genetics / Q000473:pathology; D006801:Humans; D007037:Hypothyroidism / Q000235:genetics* / Q000473:pathology; D007231:Infant, Newborn; D009687:Nuclear Proteins; D000072636:PAX8 Transcription Factor; D051761:Paired Box Transcription Factors; D010641:Phenotype; D020641:Polymorphism, Single Nucleotide; D011153:Population; D011989:Receptors, Thyrotropin / Q000235:genetics; D013961:Thyroid Gland / Q000473:pathology; D015534:Trans-Activators / Q000235:genetics
chemical_list: D004268:DNA-Binding Proteins; D009687:Nuclear Proteins; D000072636:PAX8 Transcription Factor; C083325:PAX8 protein, human; D051761:Paired Box Transcription Factors; D011989:Receptors, Thyrotropin; D015534:Trans-Activators