A novel mutation in the thyrotropin (thyroid-stimulating hormone) receptor gene in a case of congenital hypothyroidism

被引:11
作者
Jeziorowska, A. [1 ]
Pniewska-Siark, B. [1 ]
Brzezianska, E. [1 ]
Pastuszak-Lewandoska, D. [1 ]
Lewinski, A. [1 ]
机构
[1] Med Univ Lodz, Polish Mothers Mem Hosp, Res Inst, Dept Endocrinol & Metab Dis, PL-93338 Lodz, Poland
关键词
D O I
10.1089/thy.2006.16.1303
中图分类号
R5 [内科学];
学科分类号
1002 ; 100201 ;
摘要
Congenital hypothyroidism (CH) occurs approximately with a frequency of 1 in 3000-4000 births, being a disease caused by defects in thyroid hormone synthesis associated either with goiter presence or with agenesis or ectopy of the thyroid gland. A study of some familial cases has allowed identification of mutations in several known genes, including that encode the thyroid-stimulating hormone receptor (TSHR). We report a familial case of CH that transmitted as a recessive trait and caused by a novel homozygous nonsense mutation in TSHR with an initial diagnosis of thyroid agenesis hypoplasia. Genomic DNA was obtained from two siblings and their parents; TSHR was amplified using pairs of overlapping exonic primers; and polymerase chain reaction products were automatically sequenced. The propositus was homozygous (genotype: M/M) for a novel C to G transversion (1431C > G), producing a nonsense mutation, Y444X, in the first intracellular loop of TSHR, rendering a truncated receptor. Thus, the observed unresponsiveness to TSHR may be due to absent insertion of the truncated receptor into the cell membrane (if it gets translated at all) or the truncation may lead to nonsense-mediated mRNA degradation (its unresponsive to TSH). Both parents were heterozygous (wWt/M) and unrelated, as known from family history. The other daughter was homozygous for both wild-type alleles (wWt/wWt).
引用
收藏
页码:1303 / 1309
页数:7
相关论文
共 49 条
[1]   Familial congenital hypothyroidism due to inactivating mutation of the thyrotropin receptor causing profound hypoplasia of the thyroid gland [J].
Abramowicz, MJ ;
Duprez, L ;
Parma, J ;
Vassart, G ;
Heinrichs, C .
JOURNAL OF CLINICAL INVESTIGATION, 1997, 99 (12) :3018-3024
[2]   Germline mutations of TSH receptor gene as cause of nonautoimmune subclinical hypothyroidism [J].
Alberti, L ;
Proverbio, MC ;
Costagliola, S ;
Romoli, R ;
Boldrighini, B ;
Vigone, MC ;
Weber, G ;
Chiumello, G ;
Beck-Peccoz, P ;
Persani, L .
JOURNAL OF CLINICAL ENDOCRINOLOGY & METABOLISM, 2002, 87 (06) :2549-2555
[3]  
Antonarakis SE, 1998, HUM MUTAT, V11, P1
[4]   FAST AND SENSITIVE SILVER STAINING OF DNA IN POLYACRYLAMIDE GELS [J].
BASSAM, BJ ;
CAETANOANOLLES, G ;
GRESSHOFF, PM .
ANALYTICAL BIOCHEMISTRY, 1991, 196 (01) :80-83
[5]   The basolateral sorting signals of the thyrotropin and luteinizing hormone receptors:: An unusual family of signals sharing an unusual distal intracellular localization, but unrelated in their structures [J].
Beau, I ;
Groyer-Picard, MT ;
Desroches, A ;
Condamine, E ;
Leprince, J ;
Tomé, JP ;
Dessen, P ;
Vaudry, H ;
Misrahi, M .
MOLECULAR ENDOCRINOLOGY, 2004, 18 (03) :733-746
[6]  
Bogazzi F, 2000, THYROID ULTRASOUND AND ULTRASOUND-GUIDED FNA BIOPSY, P215
[7]   Genetics of specific phenotypes of congenital hypothyroidism: A population-based approach [J].
Calaciura, F ;
Miscio, G ;
Coco, A ;
Leonardi, D ;
Cisternino, C ;
Regalbuto, C ;
Bozzali, M ;
Maiorana, R ;
Ranieri, A ;
Carta, A ;
Buscema, M ;
Trischitta, V ;
Sava, L ;
Tassi, V .
THYROID, 2002, 12 (11) :945-951
[8]   Two novel mutations in the thyrotropin (TSH) receptor gene in a child with resistance to TSH [J].
CliftonBligh, RJ ;
Gregory, JW ;
Ludgate, M ;
John, R ;
Persani, L ;
Asteria, C ;
BeckPeccoz, P ;
Chatterjee, VKK .
JOURNAL OF CLINICAL ENDOCRINOLOGY & METABOLISM, 1997, 82 (04) :1094-1100
[9]   Structure-function relationships of two loss-of-function mutations of the thyrotropin receptor gene [J].
Costagliola, S ;
Sunthorntepvarakul, T ;
Migeotte, I ;
Van Sande, J ;
Kajava, AM ;
Refetoff, S ;
Vassart, G .
THYROID, 1999, 9 (10) :995-1000
[10]   Thyroid development and its disorders: Genetics and molecular mechanisms [J].
De Felice, M ;
Di Lauro, R .
ENDOCRINE REVIEWS, 2004, 25 (05) :722-746