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Identification of two mutations in a compound heterozygous child with dihydrolipoamide dehydrogenase deficiency 总被引:1,自引:0,他引:1
Hong YS; Kerr DS; Craigen WJ; Tan J; Pan Y; Lusk M; Patel MS 《Human molecular genetics》1996,5(12):1925-1930
An infant girl with elevated blood lactate, pyruvate, and plasma
branched-chain amino acids was diagnosed with dihydrolipoamide
dehydrogenase (E3; dihydrolipoamide: NAD+ oxidoreductase, EC 1.8.1.4)
deficiency. Activities of the pyruvate dehydrogenase complex and E3 from
patient were 26 and 2% of controls in blood lymphocytes, and 11 and 14% in
cultured skin fibroblasts, respectively. Western blot analysis demonstrated
that the amount of E3 protein in fibroblasts from the patient and her
father was about half of controls, while Northern blot analysis showed
normal amounts of E3 RNA. DNA sequencing of cloned full-length E3 cDNAs
from the patient revealed two mutations in separate alleles. One is a
single base insertion of an extra adenine in the last codon of the leader
peptide sequence (TAC-->TAAC) leading to a nonsense mutation which
results in the premature termination of the precursor E3 polypeptide
(Y35X). The other is a missense mutation due to substitution of guanine for
adenine, causing an Arg-->Gly substitution at amino acid 460 of the
mature protein (R460G) which triggers the loss of E3 activity probably by
structural change in the E3 dimer. DNA sequencing of E3 cDNAs from the
parents demonstrated that the nonsense mutation was inherited from the
father and the missense mutation was inherited from the mother.
相似文献
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Lesions of the articular surfaces of the knee have been managed by various techniques over the last 50 years. Surgical management has involved: excising the damaged area, refashioning the underlying bone to produce a fibrous response, and introducing allograft, autograft and synthetic materials to encourage a repair matrix. The techniques and their pitfalls are reviewed and discussed, and suggestions made as to the direction of future studies for the repair of osteochondral lesions in the painful knee. 相似文献
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WEIGHT GAIN AND REPRODUCTIVE FUNCTION: ULTRASONOGRAPHIC AND ENDOCRINE FEATURES IN ANOREXIA NERVOSA 总被引:2,自引:0,他引:2
J. L. TREASURE M. WHEELER E. A. KING P. A. L. GORDON G. F. M. RUSSELL 《Clinical endocrinology》1988,29(6):607-616
Pelvic ultrasonographic measurements and reproductive hormone levels in 36 patients with anorexia nervosa were followed as they gained weight during inpatient treatment. In 24 patients who were severely malnourished (69% of premorbid weight) the ovaries were small and amorphous and the levels of LH, FSH and oestradiol were very low. Weight gain led to the appearance of multifollicular ovaries when levels of LH and oestradiol remained low but FSH levels had increased resulting in an LH:FSH ratio of less than 1. The emergence of a dominant follicle in 19 patients after weight gain (to 97% of premorbid weight) was accompanied by an increase in uterine area and associated with increased levels of LH and oestradiol and an LH:FSH ratio greater than 2. Among these patients with a dominant follicle at peak weight, 11 menstruated within a month of discharge. The weight at which normal ovarian morphology returned was related to premorbid weight (P less than 0.002) whereas body mass index (BMI) was poorly related. Our findings suggest that pelvic ultrasonography is probably the best indicator of the weight required for full endocrine recovery and offers advantages over sequential hormonal measurements, and is valuable in the management of patients with anorexia nervosa. 相似文献
30.
OCAL L.; RUSSELL K.; BEYNON H.; CRUICKSHANK K.; LANCHBURY J. S.; WALPORT M.; ISENBERG D.; BRIGGS D. 《Rheumatology (Oxford, England)》1996,35(6):529-533
The aim of this study was to determine whether the TAP2 (Transporterassociated with Antigen Processing 2) locus is involved in susceptibilityto systemic lupus erythematosus (SLE). We adopted the interethnicapproach to overcome problems in the analysis resulting fromlinkage disequilibrium. The TAP2 gene polymorphisms of the codonscorresponding to amino acid positions 379, 565 and 665 wereinvestigated by amplification refractory mutation system polymerasechain reaction (ARMS-PCR) in 186 patients (151 white Europeans,35 Afrocaribbeans) and 183 controls (79 white Europeans, 104Afrocaribbeans). In the European SLE patients, the frequencyof the TAP2 type V-A-TA was marginally lower compared with thecontrol group (31% vs 42%), with negative linkage disequilibriumbetween this TAP2 type and DR3 probably accounting for the difference.For the European SLE patients, we confirmed a significant associationof DR3 with disease status [odds ratio = 4.16, 95% confidenceinterval (CI), 2.088.39] and in the patients with DR3there was a significantly high frequency of the TAP2 type V-A-T-.In the Afrocaribbean SLE patients, any associations of diseasestatus with TAP2 phenotype were the inverse of those in theEuropean patients. Thus, in these patients the frequency ofV-A-TA was higher than in controls (46% vs 26%, OR = 2.4, 95%CI 1.015.74), while the frequency of V-A-T- was lower(26% vs 40%, not significant). Despite possible sampling error,the lack of a difference in TAP2 status between cases and controlswithin ethnic groups and, if anything, an inverse associationacross ethnic groups, makes it unlikely that the TAP2 polymorphismstudied here is of primary relevance to SLE susceptibility. KEY WORDS: MHC, TAP2, SLE, Interethnic 相似文献