A 3-base pair deletion,c.9711_9713del,in DMD results in intellectual disability without muscular dystrophy

We have identified a deletion of 3 base pairs in the dystrophin gene (DMD), c.9711_9713del, in a family with nonspecific X-linked intellectual disability (ID) by sequencing of the exons of 86 known X-linked ID genes. This in-frame deletion results in the deletion of a single-amino-acid residue, Leu3238, in the brain-specific isoform Dp71 of dystrophin. Linkage analysis supported causality as the mutation was present in the 7.6 cM linkage interval on Xp22.11–Xp21.1 with a maximum positive LOD score of 2.41 (MRX85 locus). Molecular modeling predicts that the p.(Leu3238del) deletion results in the destabilization of the C-terminal domain of dystrophin and hence reduces the ability to interact with β-dystroglycan. Correspondingly, Dp71 protein levels in lymphoblastoid cells from the index patient are 6.7-fold lower than those in control cell lines (P=0.08). Subsequent determination of the creatine kinase levels in blood of the index patient showed a mild but significant elevation in serum creatine kinase, which is in line with impaired dystrophin function. In conclusion, we have identified the first DMD mutation in Dp71 that results in ID without muscular dystrophy.     

Comparing deaf and hearing Dutch infants: Changes in the vowel space in the first 2 years

The influence of the mother tongue on vowel productions in infancy is different for deaf and hearing babies. Audio material of five hearing and five deaf infants acquiring Dutch was collected monthly from month 5–18, and at 24 months. Fifty unlabelled utterances were digitized for each recording. This study focused on developmental paths in vowel productions. The applied automated band filtering analysis is F₀‐independent and results in a spectral envelope, sampled in a 40‐dimensional space. Via a Principal Component Analysis (PCA, data reduction), a vowel space for normally hearing 2‐year‐olds was constructed, enabling the projection of the individual developmental data of the infants in a two‐dimensional reference plane. Comparison of the results for the hearing and the deaf infants over 2 years indicates individual as well as group differences. The amount of hearing loss as well as the communication styles seem to be important factors in explaining differences between the infant categories.     

Sex Differences in Cardiac Electrophysiology and Clinical Arrhythmias: Epidemiology,Therapeutics, and Mechanisms

Sex differences in cardiac electrophysiological properties and arrhythmias are evident in epidemiologic and investigative studies as well as in daily patient care. At the supraventricular level, women are at increased risk of sick sinus syndrome and atrioventricular (AV) node re-entrant tachycardia, whereas men manifest more AV block and accessory pathway–mediated arrhythmias. At the ventricular level, women are generally at higher risk of long QT–associated arrhythmias, whereas men are more likely to present with early repolarization, idiopathic ventricular fibrillation, and Brugada syndromes. Great advances have been made in unraveling the fundamental mechanisms underlying sex differences in ventricular arrhythmias, particularly those associated with abnormal repolarization. Conversely, the basis for male-predominant arrhythmia risk in structural heart disease and differences in supraventricular arrhythmia susceptibility are poorly understood. Beyond biological differences, arrhythmia occurrence and patient care decisions are also influenced by gender-related factors. This article reviews the current knowledge regarding the nature and underlying mechanisms of sex differences in basic cardiac electrophysiology and clinical arrhythmias.