Stone composition, metabolic profile and the presence of the gut-inhabiting bacterium oxalobacter formigenes as risk factors for renal stone formation

To examine stone composition, metabolic evaluation and colonization of Oxalobacter formigenes as risk factors for renal stone formation. Subjects and Eighty patients with renal stones and 70 healthy controls were enrolled in the study. Of the 80 patients, 48 were first-time stone formers [FSF] and 32 were 'recurrent' stone formers [RSF], recurrent indicating 2 or more episodes of stone formation. Stone analysis by X-ray crystallography, 24-hour urine metabolic profile and detection of O. formigenes-specific DNA by PCR were performed for each patient. Detection of O. formigenes was also performed on 45 and urinary metabolic profile on an additional 25 controls. Calcium oxalate monohydrate was the major component of stones, hyperoxaluria and hypocitraturia were the most common urinary abnormalities in the 80 patients, 46% of RSF patients had hypercalciuria. Urinary abnormalities were far less frequent in the controls, with the exception of hypocitraturia [40%]. Of the urinary metabolites, only calcium levels were significantly different [p < 0.05] between FSF [6.50 +/- 4.08 mmol/24 h] and RSF [8.21 +/- 5.26 mmol/24 h] patients. Colonization of O. formigenes was higher in controls [62.2%] than in FSF [33.3%] or RSF [28%] patients, it was least in patients with more than 4 episodes [7%] of stone formation. The findings indicate that lack of colonization of O. formigenes may be an important risk factor for recurrence of stone formation [calcium oxalate monohydrate]

De novo mutations in sporadic deletional Duchenne muscular dystrophy (DMD) cases

Dinucleotide repeat polymorphism based genetic analysis is a powerful approach to gain insight into rare genetic events like germline mosaicism and de novo mutations. The loss of heterozygosity of polymorphic dinucleotide loci at "deletional hotspot" of dystrophin gene can provide direct evidence of carrier status in female relatives of affected DMD patients with overlapped exonic deletions. We have used 4 STR loci of the central deletional hotspot of the dystrophin gene for genetic analysis in sporadic unrelated DMD families. Twenty-nine mothers of sporadic deletional cases were analysed and their carrier status was determined. Eighteen of them showed heterozygosity in the deleted loci suggesting the occurrence of de novo mutations. In 9 cases, the carrier status was indeterminate while 2 showed germline mosaicism. Our observations reiterated the importance of STR analysis in determining the status of mothers of sporadic deletional DMD cases in order to provide proper genetic counselling.