PMID- 10199795
OWN - NLM
STAT- MEDLINE
DCOM- 19990421
LR  - 20041117
IS  - 0021-972X (Print)
IS  - 0021-972X (Linking)
VI  - 84
IP  - 4
DP  - 1999 Apr
TI  - A germline mutation of the thyrotropin receptor gene associated with
      thyrotoxicosis and mitral valve prolapse in a Chinese family.
PG  - 1459-62
AB  - Activating mutations of the TSH receptor (TSH-R) have been reported to result in 
      toxic adenomas, multinodular goiters, sporadic neonatal hyperthyroidism, and
      familial autosomal dominant nonautoimmune hyperthyroidism. To date, all
      descriptions of such mutations, whether somatic or genomic, have been confined to
      the Caucasian population. We describe a Chinese family in whom a germline proline
      to serine substitution in position 639 resulted in familial thyrotoxicosis. This 
      constitutively activating mutation has been previously described in a
      hyperfunctioning thyroid nodule. The three children in this family developed
      thyrotoxicosis during childhood; their father was diagnosed as thyrotoxic at the 
      age of 38 yr. Two of the children and the father had mitral valve prolapse (MVP) 
      associated with mitral regurgitation. There was a close temporal relationship
      between the onset of thyrotoxicosis and the diagnosis of mitral valvular disease 
      in these patients. An increased prevalence of MVP has been reported in Graves'
      disease and chronic lymphocytic thyroiditis, but the pathophysiological
      mechanisms linking MVP and autoimmune thyroid disease are still not understood.
      This is the first report of an association between activating TSH-R mutations and
      MVP. We postulate that TSH-R activation may increase the clinical expression of
      MVP in genetically predisposed individuals.
FAU - Khoo, D H
AU  - Khoo DH
AD  - Department of Endocrinology, Singapore General Hospital, Singapore.
      daphnevkhoo@sgh.gov.sg
FAU - Parma, J
AU  - Parma J
FAU - Rajasoorya, C
AU  - Rajasoorya C
FAU - Ho, S C
AU  - Ho SC
FAU - Vassart, G
AU  - Vassart G
LA  - eng
PT  - Case Reports
PT  - Journal Article
PL  - United States
TA  - J Clin Endocrinol Metab
JT  - The Journal of clinical endocrinology and metabolism
JID - 0375362
RN  - 0 (Receptors, Thyrotropin)
SB  - IM
CIN - J Clin Endocrinol Metab. 1999 Sep;84(9):3404-5. PMID: 10487723
MH  - Adult
MH  - Child
MH  - Child, Preschool
MH  - Female
MH  - Genetic Predisposition to Disease
MH  - *Germ-Line Mutation
MH  - Humans
MH  - Male
MH  - Mitral Valve Prolapse/etiology/*genetics
MH  - Receptors, Thyrotropin/*genetics
MH  - Thyrotoxicosis/etiology/*genetics
EDAT- 1999/04/13 00:00
MHDA- 1999/04/13 00:01
CRDT- 1999/04/13 00:00
PHST- 1999/04/13 00:00 [pubmed]
PHST- 1999/04/13 00:01 [medline]
PHST- 1999/04/13 00:00 [entrez]
AID - 10.1210/jcem.84.4.5620 [doi]
PST - ppublish
SO  - J Clin Endocrinol Metab. 1999 Apr;84(4):1459-62. doi: 10.1210/jcem.84.4.5620.