A new X-linked mental retardation (XLMR) syndrome with late-onset primary testicular failure, short stature and microcephaly maps to Xq25-q26

X-linked mental retardation (XLMR) is a heterogeneous disorder with both syndromic and non-syndromic forms. Here we describe the clinical and molecular characterisation of a family with a syndromic form of XLMR with hypogonadism and short stature. We investigated a family in which four male members in two generations presented with hypergonadotrophic hypogonadism associated with development of small and abnormal testes. In two of the males, late-onset testicular ascent was noted. In addition, all affected males had short stature (<0.4th centile) and mild learning difficulties and three out of the four had microcephaly. Karyotypes were normal and endocrine investigations confirmed primary testicular failure. The phenotype segregated as an X-linked trait. Haplotype and genetic two-point linkage analysis with 22 microsatellites excluded the whole X chromosome except for a region on Xq25-Xq27 encompassing 13.7Mb with a maximum LOD score of 1.1 for marker DXS8038 at theta=0.05. One family previously described as having XLMR with hypogonadism and short stature maps to the same X chromosome region implicated in our family. However, the more severe mental retardation, muscle wasting and tremor described in this other family would suggest that our family is affected by a novel XLMR syndrome.     

Detection of genomic deletions of PKP2 in arrhythmogenic right ventricular cardiomyopathy

Arrhythmogenic right ventricular cardiomyopathy (ARVC) is an inherited myocardial disease that predominantly affects the right ventricle and is associated with ventricular arrhythmias that may lead to sudden cardiac death. Mutations within at least seven separate genes have been identified to cause ARVC, however a genetic culprit remains elusive in approximately 50% of cases. Although negative genetic testing may be secondary to pathogenic mutations within undiscovered genes, an alternative explanation may be the presence of large deletions or duplications involving known genes. These large copy number variants may not be detected with standard clinical genetic testing which is presently limited to direct DNA sequencing. We describe two cases of ARVC possessing large deletions involving plakophilin‐2 (PKP2) identified with microarray analysis and/or multiplex ligation‐dependent probe amplification (MLPA) that would have been classified as genotype negative with standard clinical genetic testing. A deletion of the entire coding region of PKP2 excluding exon 1 was identified in patient 1 and his son. In patient 2, MLPA analysis of PKP2 revealed deletion of the entire gene with subsequent microarray analysis demonstrating a de novo 7.9 Mb deletion of chromosome 12p12.1p11.1. These findings support screening for large copy number variants in clinically suspected ARVC cases without clear disease causing mutations following initial sequencing analysis.     

Comparison of digital systems and conventional dental film for the detection of approximal enamel caries

Objectives

The aims of this study were (1) to compare the accuracy of the detection of approximal enamel caries lesions using three intraoral storage phosphor plate digital systems and one conventional film-based radiographic system; and (2) to determine whether there is a correlation between the histological and radiographic measurements of enamel caries.

Methods

160 approximal surfaces were radiographed under standardized conditions using three storage phosphor stimulable systems (DenOptix and Digora FMX with white and blue plates), and one film system (Insight film). 17 observers scored the images for the presence and depth of caries using a 4-point scale. The presence of caries was validated histologically (gold standard). Two-way analysis of variance was used to test the differences in sensitivity, specificity and overall accuracy (TP + TN). The data from the radiographic and histological measurements were statistically analysed by Spearman’s rank correlation coefficient.

Results

Two-way analysis of variance and the post hoc t-test demonstrated that Digora (white plate) had higher specificity and overall accuracy values than DenOptix (P = 0.021); there was no statistically significant difference among the other imaging modalities (P > 0.05). There was no significant correlation between the histological depth measurements and the radiographic measurements from Digora (blue plate) (P = 0.43), Digora (white plate) (P = 0.15), DenOptix (P = 0.17) and Insight film (P = 0.06).

Conclusions

The results suggest that (1) the performance of the three storage phosphor image plate systems was similar to that of the Insight film for detection of approximal enamel caries, and (2) the increase in histological depth of enamel caries was not significantly correlated with radiographic measurements.     

Use of CO2 to move structures as an aid to percutaneous procedures

By injecting small amounts of CO2 through a needle, one can move bowel or bladder from the intended path of instruments during interventional procedures. The technique worked well in six of seven cases in the pelvis and retroperitoneum; it was not effective in the mediastinum or midabdomen (n = 6).     

Sequelae of acute renal infections: CT evaluation

Seventeen patients with upper urinary tract infection who underwent 51 computed tomographic studies (two to five per patient; mean, three) were retrospectively evaluated. Five to 10 days after the initial examination, there was little change in parenchymal abnormalities, but perirenal inflammation worsened and then subsided over 2-8 weeks. Enlargement of the affected kidney, present initially in 12 patients, persisted up to 6 weeks and resolved by 10-16 weeks. Abnormalities of parenchymal contrast material enhancement persisted for 1-2 months. New cortical scars appeared in six of 12 patients with an initially normal renal contour and in one of five patients who had scars initially. Three patients with a renal abscess developed a new calyceal diverticulum, presumably by rupture of the abscess into the collecting system. The present study shows that abnormalities of renal size and enhancement persist for weeks to months after clinical signs of infection resolve and that scarring in adults with urinary tract infection occurs more frequently than was previously realized.     

Successful renal transplantation in a family with a novel mutation in COL4A3 gene and autosomal recessive Alport syndrome

Alport syndrome (AS) is an inherited disorder of basement membranes caused by mutations affecting specific proteins of the type IV collagen family, presenting with nephropathy and extrarenal manifestations such as sensorineural deafness and ocular anomalies. Ten percentage to 15% of the patients with AS have autosomal recessive (ARAS) due to mutation in either COL4A3 or COL4A4 gene. We report a novel mutation in the COL4A3 gene in an Indian family with ARAS. The above‐mentioned genetic anomaly was a missense variation in exon 26 of the COL4A3 gene (chr2:228137797G>A; c.1891G>A) that resulted in the amino acid substitution of Arginine for Glycine at codon 631 (p.Gly631Arg) that was present in the heterozygous state in the asymptomatic parents and homozygous state in the male offspring who presented with early‐onset end‐stage renal disease, lenticonus and hearing loss. The patient (male offspring) underwent successful renal transplantation with his mother as a donor.