Characterization of greater middle eastern genetic variation for enhanced disease gene discovery

The Greater Middle East (GME) has been a central hub of human migration and population admixture. The tradition of consanguinity, variably practiced in the Persian Gulf region, North Africa, and Central Asia1-3, has resulted in an elevated burden of recessive disease4. Here we generated a whole-exome GME variome from 1,111 unrelated subjects. We detected substantial diversity and admixture in continental and subregional populations, corresponding to several ancient founder populations with little evidence of bottlenecks. Measured consanguinity rates were an order of magnitude above those in other sampled populations, and the GME population exhibited an increased burden of runs of homozygosity (ROHs) but showed no evidence for reduced burden of deleterious variation due to classically theorized ‘genetic purging’. Applying this database to unsolved recessive conditions in the GME population reduced the number of potential disease-causing variants by four- to sevenfold. These results show variegated genetic architecture in GME populations and support future human genetic discoveries in Mendelian and population genetics

Sleep physiology and sleep disorders in childhood

Hanan M El ShakankiryKing Fahd University Hospital, Al Dammam University, Al Khobar, Kingdom of Saudi ArabiaAbstract: Sleep has long been considered as a passive phenomenon, but it is now clear that it is a period of intense brain activity involving higher cortical functions. Overall, sleep affects every aspect of a child's development, particularly higher cognitive functions. Sleep concerns are ranked as the fifth leading concern of parents. Close to one third of all children suffer from sleep disorders, the prevalence of which is increased in certain pediatric populations, such as children with special needs, children with psychiatric or medical diagnoses and children with autism or pervasive developmental disorders. The paper reviews sleep physiology and the impact, classification, and management of sleep disorders in the pediatric age group.Keywords: sleep physiology, sleep disorders, childhood, epileps

Resolution of international litigation by the electronic arbitration

L'environnement numérique et les échanges électroniques accélèrent et participent à la mondialisation et à la globalisation de l'économie, et par là multiplient la dimension internationale dans les litiges, tout en générant sans cesse de nouveaux problèmes juridiques. Des modes électroniques de règlement des litiges apparaissent afin de faire face à ce nouveau monde dont l'arbitrage électronique. Ce moyen de règlement, même s'il est techniquement praticable, juridiquement soulève nombre de questions : d'une part, l'arbitrage classique exige de nombreuses conditions de forme et de fond que l'arbitrage électronique par sa nature même ne peut totalement satisfaire ; d'autre part, la procédure arbitrale totalement dématérialisée présente des difficultés biens distinctes. Afin de surmonter ces difficultés, il faut présenter les textes juridiques régissant les procédures arbitrales traditionnelles et les confronter aux procédures arbitrales électroniques. De cette confrontation se dégageront les particularités de l'arbitrage électronique comme mode alternatif de règlement des litiges du commerce international en général, et électronique en particulier.The digital environment and electronic exchanges contribute and accelerate globalization, and thus multiplies the international dimension in litigation, while constantly generating new legal problems. Electronic arbitration is a form of alternative dispute resolution. Even if it is technically feasible, it raises many legal issues. On the one hand, the classic arbitration requires many forms conditions that the electronic arbitration cannot totally satisfy. On the other hand, the fully dematerialized arbitration presents distinct properties.To overcome these difficulties, we should present the legal texts governing the classic arbitration and compare it with the electronic arbitration procedures. This allows us to identify the features of electronic arbitration as an alternative dispute resolution of the international commercial disputes and especially electronics

Pattern sensitivity: a missed part of the diagnosis

Hanan M El Shakankiry,1 Ann A Abdel Kader21Department of Pediatrics, King Fahd University Hospital–Al Dammam University, Al Khobar, Kingdom of Saudi Arabia; 2Department of Clinical Neurophysiology, Kasr Aini Hospitals–Cairo University, Cairo, EgyptRationale: Pattern sensitivity can be diagnosed by presenting a series of visual patterns to the subject in the electroencephalography (EEG) laboratory; however, testing for pattern sensitivity is not routinely done during EEG recording. This work aimed to highlight the incidence of pattern sensitivity among patients referred for routine EEG recording during a 1-year period, identifying the cause of referral, diagnosis, and the characteristics of pattern-sensitive patients.Methods: All patients aged 4 years and older who were referred for routine EEG during a 12-month period and had no motor or visual impairment were enrolled in the study. Intermittent photic stimulation and pattern sensitivity were tested for each case. Pattern sensitivity was tested by scanning three different rhythmically moving patterns at reading distance with the patient seated in an illuminated room. A pattern evoking a paroxysmal response was reintroduced after exposure to a blank white card to confirm the findings.Results: Two hundred twenty-eight patients were studied; twelve patients (5.26%) had pattern sensitivity and their ages ranged from 5 to 12 years. Eight of these patients (66.7%) were referred for seizure disorders, two were referred with the diagnosis of migraine, one with headache and poor scholastic performance and one with recurrent attacks of dizziness for investigation. Seven of the twelve patients (58.3%) had a previous EEG done without testing for pattern sensitivity. Five patients (41.6%) had positive family history for epilepsy, three (25%) for migraine, and two (16.6%) for migraine and epilepsy. Two patients (16.6%) had pattern sensitivity without photosensitivity. Pattern stimulation provoked epileptiform discharges in eight patients (66.6%), focal discharges in one, and unilateral build-up of posterior discharge in three.Conclusion: Diagnosis of pattern sensitivity is often missed as it is not routinely tested for during EEG recording. The result of the study challenges the concept of a consistent association between photosensitivity and pattern sensitivity; it also raises questions about the incidence of pattern sensitivity among children who do not suffer from epilepsy and in particular those with migraine, headache and scholastic difficulties. Further studies are therefore needed to clarify the phenotypic spectrum of this EEG trait.Keywords: reflex epilepsy, pattern sensitivity, migraine, headach

Mutations in ALDH1A3 represent a frequent cause of microphthalmia/anophthalmia in consanguineous families.

Anophthalmia or microphthalmia (A/M), characterized by absent or small eye, can be unilateral or bilateral and represent developmental anomalies due to the mutations in several genes. Recently, mutations in aldehyde dehydrogenase family 1, member A3 (ALDH1A3) also known as retinaldehyde dehydrogenase 3, have been reported to cause A/M. Here, we screened a cohort of 75 patients with A/M and showed that mutations in ALDH1A3 occurred in six families. Based on this series, we estimate that mutations in ALDH1A3 represent a major cause of A/M in consanguineous families, and may be responsible for approximately 10% of the cases. Screening of this gene should be performed in a first line of investigation, together with SOX2