TY - JOUR
T1 - Genetics of specific phenotypes of congenital hypothyroidism
T2 - A population-based approach
AU - Calaciura, Francesca
AU - Miscio, Giueppe
AU - Coco, Angelo
AU - Leonardi, Daniela
AU - Cisternino, Carmela
AU - Regalbuto, Concetto
AU - Bozzali, Maura
AU - Maiorana, Raffaella
AU - Ranieri, Annalisa
AU - Carta, Anna
AU - Buscema, Massimo
AU - Trischitta, Vincenzo
AU - Sava, Lidia
AU - Tassi, Vittorio
PY - 2002/11/1
Y1 - 2002/11/1
N2 - 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 (1277insGGCC) was present; in two other cases mutations not previously described (1996G → T and 2295G → 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 (1277insGGCC) and the other from the father (1996G → T, Glu → Stop). In the latter group (n = 8), a patient with a 16-base pair C(T)13CC deletion in TSHR gene intron 8, 42-bp distal to exon/intron 8 splice junction, was identified. No mutation was identified in Pax8 gene.
AB - 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 (1277insGGCC) was present; in two other cases mutations not previously described (1996G → T and 2295G → 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 (1277insGGCC) and the other from the father (1996G → T, Glu → Stop). In the latter group (n = 8), a patient with a 16-base pair C(T)13CC deletion in TSHR gene intron 8, 42-bp distal to exon/intron 8 splice junction, was identified. No mutation was identified in Pax8 gene.
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M3 - Article
C2 - 12490071
AN - SCOPUS:6444245853
VL - 12
SP - 945
EP - 951
JO - Thyroid
JF - Thyroid
SN - 1050-7256
IS - 11
ER -