Inactivating mutations of THRB, which encodes the thyroid hormone receptor β (TRβ), cause
resistance to thyroid hormone (RTH; OMIM 190160). To date, more than 100 THRB mutations have
been reported among RTH patients. Most mutations substitute a single amino-acid residue in the ligand-binding
domain. In this report, we describe clinical and molecular findings of three families with RTH. Three families
harbored one novel (p.I431M) and two recurrent (p.R320H and p.R383C) THRB mutations. To
examine the pathogenicity of identified mutations, we introduced a novel computational mutation prediction
method based on three-dimensional structure data of TRβ-T3 complex. First, to define the accuracy
of our prediction system, we evaluated ten previously reported ‘positive control’ mutations, as well as 30
seemingly benign sequence variations observed among vertebral species as ‘negative controls’. We found that
our system had a sensitivity of 80% and a specificity of 93%. We then analyzed three mutations detected in the
present study and found that all three mutations are predicted to be deleterious. Our data suggest that our
structure-based prediction system would be a prompt, inexpensive and feasible method for evaluating the
pathogenicity of missense THRB mutations.
Nontyphoidal Salmonella (NTS) encephalopathy is characterized by rapidly progressive brain dysfunction that develops after NTS enteritis. The mechanism of central nervous system involvement remains unclear. We examined cerebrospinal fluids from 7 patients for cytokines and found elevated interleukin-6, interleukin-8, and monocyte chemotactic protein-1 concentrations in all the patients, suggesting that the proinflammatory cytokines are involved in the pathogenesis of NTS encephalopathy.
We report a case of asynchronous occurrence of bilateral adrenocortical adenoma in a
13-yr-old girl with Beckwith-Wiedemann syndrome. A right virilizing adrenal adenoma was
surgically removed at age 6, following clinical manifestation of virilization such as
acne, voice change, clitoris hypertrophy and overgrowth. Histopathological examination of
the resected specimen revealed an adrenocortical adenoma predominantly composed of
eosinophilic tumor cells expressing all the steroidogenic enzymes. High serum levels of
DHEA-S (6,380 ng/ml) and testosterone (547 ng/dl) were noted prior to the operation.
Postoperative course was unremarkable. Menstruation started at age 11, with a regular
interval. At the age of 13 yr old, a high serum level of DHEA-S (8,250 ng/ml) was
detected. In contrast to the episode of virilization at age 6, however, the serum
testosterone level was not so high (122 ng/dl), and no clinical symptoms of virilization
were apparent. Abdominal ultrasonography demonstrated the presence of a left
adrenocortical adenoma. Pathological examination of the resected specimen revealed a
circumscribed and well encapsulated tumor with essentially the same histological features
as the tumor previously removed, except that the tumor cells showed a more prominent
morphological similarity to the fetal adrenal cortex and did not express
3β HSD. The absence of virilization at the second episode was due to
the relatively low serum level of testosterone compared with that of DHEA-S.
Abstract. We report on two patients with 45,X/46,X,idic(Y) who showed different sex development. Case 1 is a 2-year-old boy. At one month of age his left retentio testis was noticed. Orchidopexy of left side was attempted when the patient was one year old, but gonadectomy was performed instead because an undifferentiated gonad was found. Pathological examination revealed ovotestis. Physical examination showed short stature (-2.6 SD), right testis (1 ml in volume), small penis (2.5 cm in length), and no signs of Turner syndrome. Chromosome analysis for peripheral lymphocytes revealed 45, X[5]/46, X, +mar [25].ish idic (Y) (q11.2) (SRY++, DYZ3++, DYZ1-). An HCG test showed a fairly good testosterone response (14→182 ng/dL). Case 2 is an 11-year-old girl. Physical examination showed short stature (-2.5 SD) and no signs of Turner syndrome. An LH-RH test showed excessive response (LH 36→400; FSH 200→480 mIU/mL). Small uterus was detected by abdominal echography. Because of the risk of gonadoblastoma, gonadectomy was performed. The bilateral gonads were streak gonads. Chromosome analysis of the resected gonad revealed 45, X[27]/46, X, idic (Y) (q12) [23]. PCR analysis of DNA from the resected gonad detected SRY. Since the rearranged Y chromosomes of both cases were positive for SRY, it is likely that the difference in the mosaic cell ratio in the gonad played an important role in their discordant sexual phenotypes.
scite is a Brooklyn-based organization that helps researchers better discover and understand research articles through Smart Citations–citations that display the context of the citation and describe whether the article provides supporting or contrasting evidence. scite is used by students and researchers from around the world and is funded in part by the National Science Foundation and the National Institute on Drug Abuse of the National Institutes of Health.