The 3q29 microdeletion syndrome: report of three new unrelated patients and in silico "RNA binding" analysis of the 3q29 region

The human 3q29 microdeletion syndrome is associated with mild facial dysmorphism, developmental delay and variable congenital malformations. We report three new unrelated patients with this syndrome. We also performed in silico RNA binding analysis in silico on the 3q29 critical region genes. Several genes within this genomic region including DLG1 and RNF168 are predicted to bind RNA. While recessive mutations in RNF168 cause RIDDLE syndrome, an immune deficiency and radiosensitivity disorder, the potential impact of heterozygous deletion of RNF168 on patients with the 3q29 deletion syndrome is still unknown.     

Diabetes mellitus type 2 and other chronic non-communicable diseases in the central region,Saudi Arabia (riyadh cohort 2): a decade of an epidemic

Background

Follow-up epidemiologic studies are needed to assess trends and patterns of disease spread. No follow-up epidemiologic study has been done in the Kingdom of Saudi Arabia to assess the current prevalence of major chronic, noncommunicable diseases, specifically in the urban region, where modifiable risk factors remain rampant. This study aims to fill this gap.

Methods

A total of 9,149 adult Saudis ages seven to eighty years (5,357 males (58.6%) and 3,792 females (41.4%)) were randomly selected from the Riyadh Cohort Study for inclusion. Diagnosis of type 2 diabetes mellitus (DMT2) and obesity were based on the World Health Organization definitions. Diagnoses of hypertension and coronary artery disease (CAD) were based on the Seventh Joint National Committee on Prevention, Detection, Evaluation, and Treatment of High Blood Pressure and American Heart Association criteria, respectively.

Results

The overall crude prevalence of DMT2 was 23.1% (95% confidence interval (95% CI) 20.47 to 22.15). The age-adjusted prevalence of DMT2 was 31.6%. DMT2 prevalence was significantly higher in males, with an overall age-adjusted prevalence of 34.7% (95% CI 32.6 to 35.4), than in females, who had an overall age-adjusted prevalence of 28.6% (95% CI 26.7 to 29.3) (P < 0.001). The overall crude prevalence of obesity was 31.1% (95% CI 30.1 to 32.0). The age-adjusted prevalence of obesity was 40.0%. The prevalence of obesity was higher in females, with an overall prevalence of 36.5% (95% CI 35.1 to 37.83), than in males (25.1% (95% CI 23.7 to 26.3)) (P < 0.001). The age-adjusted prevalence of hypertension and CAD were 32.6% (95% CI 31.7 to 33.6) and 6.9% (95% CI 6.4 to 7.4), respectively.

Conclusion

Comparisons of our findings with earlier data show that the prevalence of DMT2, hypertension and CAD in Riyadh, Saudi Arabia, has alarmingly worsened. Aggressive promotion of public awareness, continued screening and early intervention are pivotal to boosting a positive response.

     

Ocular motility problems associated with sumatriptan administration

In a 55-year-old woman with classic migraine, paresis of the superior division of the right oculomotor nerve occurred twice after subcutaneous injections of sumatriptan. Each paresis disappeared within 2 weeks. Magnetic resonance imaging of the head was normal. Sumatriptan injections were discontinued, and ocular motility problems ceased. Use of sumatriptan for migraine should be considered in the diagnosis of transient, pupil-sparing, oculomotor nerve palsies in the absence of other microvascular risk factors.     

The many faces of peroxisomal disorders: Lessons from a large Arab cohort

Defects in the peroxisomes biogenesis and/or function result in peroxisomal disorders. In this study, we describe the largest Arab cohort to date (72 families) of clinically, biochemically and molecularly characterized patients with peroxisomal disorders. At the molecular level, we identified 43 disease-causing variants, half of which are novel. The founder nature of many of the variants allowed us to calculate the minimum disease burden for these disorders in our population ~1:30 000, which is much higher than previous estimates in other populations. Clinically, we found an interesting trend toward genotype/phenotype correlation in terms of long-term survival. Nearly half (40/75) of our peroxisomal disorders patients had documented survival beyond 1 year of age. Most unusual among the long-term survivors was a multiplex family in which the affected members presented as adults with non-specific intellectual disability and epilepsy. Other unusual presentations included the very recently described peroxisomal fatty acyl-CoA reductase 1 disorder as well as CRD, spastic paraparesis, white matter (CRSPW) syndrome. We conclude that peroxisomal disorders are highly heterogeneous in their clinical presentation. Our data also confirm the demonstration that milder forms of Zellweger spectrum disorders cannot be ruled out by the “gold standard” very long chain fatty acids assay, which highlights the value of a genomics-first approach in these cases.     

Pallido-pyramidal degeneration, supranuclear upgaze paresis and dementia: Kufor-Rakeb syndrome

An unusual neurological syndrome in an Arab family with five affected siblings, is reported. Autosomal recessive inheritance is suggested by having multiple affected siblings born to phenotypically normal consanguineous parents. Similar to Davison's Pallido-pyramidal syndrome, they presented with the clinical signs and symptoms of severe parkinsonism as well as evidence of cortico-spinal tract disease. In addition, they had dementia and supranuclear upgaze paresis. MRI studies showed significant atrophy of the globus pallidus and the pyramids, as well as generalized brain atrophy in later stages. Therapy with levodopa resulted in significant improvement in the extrapyramidal dysfunction. We suggest that this probably represents a new syndrome which is closely related but not identical to the pallido-pyramidal syndrome.