Genetic analysis of TTF-2 gene in children with congenital hypothyroidism and cleft palate, congenital hypothyroidism, or isolated cleft palate.
Homozygous null mice for thyroid transcription factor (TTF)-2 gene exhibit cleft palate and thyroid malformation. We performed a genetic analysis of the TTF-2 gene in 2 children with congenital hypothyroidism (CH) and cleft palate, 45 children with thyroid dysgenesis, 19 children with isolated cleft palate or cleft lip, 4 patients with thyroid hemiagenesis. The entire coding-region of the TTF-2 gene was analyzed by direct sequencing. Direct sequencing of the TTF-2 gene revealed polymorphisms in the length of the polyalanine tract. The most frequent stretch length was 14 residues and it was found in 50 of 70 (71%) and in 45 of 53 (85%) normal healthy controls. A polyalanine tract of 16 residues in the heterozygous state was seen in 18 of 70 (26%) cases and in 4 of 53 (7%) normal subjects. In 1 of 4 (25%) case of hemiagenesis a polyalanine tract of 16 residues in the homozygous state was observed. In 1 of 26 agenesis the polyalanine tract consisted of 12 residues in the heterozygous state. Direct sequencing also revealed the presence of two silent polymorphisms. No mutations were identified in the TTF-2 gene. In conclusion, our results show that no genetic alteration was present in the TTF-2 gene of these patients, suggesting that defects in the TTF-2 gene are a rare event.
Dipartimento di Endocrinologia e Metabolismo e Centro Eccellenza AmbiSEN, Università di Pisa, Pisa, Italy. mtonacchera@hotmail.com
Massimo
M
Tonacchera
Mariaelena
M
Banco
Paola
P
Lapi
Caterina
C
Di Cosmo
Anna
A
Perri
Lucia
L
Montanelli
Lidia
L
Moschini
Gianluca
G
Gatti
Daniele
D
Gandini
Alessandro
A
Massei
Patrizia
P
Agretti
Giuseppina
G
De Marco
Paolo
P
Vitti
Luca
L
Chiovato
Aldo
A
Pinchera
D000293:Adolescent; D000328:Adult; D001483:Base Sequence; D002648:Child; D002675:Child, Preschool; D002972:Cleft Palate / Q000150:complications / Q000235:genetics*; D003409:Congenital Hypothyroidism; D004268:DNA-Binding Proteins / Q000235:genetics*; D005260:Female; D051858:Forkhead Transcription Factors; D006801:Humans; D007037:Hypothyroidism / Q000150:complications / Q000235:genetics*; D007223:Infant; D008297:Male; D008969:Molecular Sequence Data; D011110:Polymorphism, Genetic; D012097:Repressor Proteins / Q000235:genetics*
D004268:DNA-Binding Proteins; C106894:FOXE1 protein, human; D051858:Forkhead Transcription Factors; D012097:Repressor Proteins