Case Report: Clinical delineation of CACNA1D mutation: New cases and literature review.

Background: Calcium ions are involved in several human cellular processes; nevertheless, the relationship between calcium channelopathies (CCs) and autism spectrum disorder (ASD) or intellectual disability (ID) has been previously investigated. We delineate the spectrum of clinical phenotypes and the symptoms associated with a syndrome caused by an inherited gain-of-function mutation in CACNA1D in a family with a history of neuropsychiatric disorders. We also review the clinical and molecular phenotype of previously reported variants of CACNA1D. Case presentation: We report the case of a 9-year-old female patient, diagnosed with ASD, severe ID, hyperactivity, and aggressive impulsive behaviors. The father, who was a 65-year-old at the time of his death, had ID and developed major depressive disorder with catatonic features and nihilistic delusion, followed by rapidly progressive dementia. He died after experiencing prolonged seizures followed by post-cardiac arrest. The patient's sister was a 30-year-old woman, known to have a severe ID with aggressive behaviors and sleep disorders. The sister has been diagnosed with bipolar disorder and psychosis. Through whole exome sequencing, a heterozygous previously identified and functionally characterized missense likely pathogenic variant was identified in the CACNA1D gene NM_001128840.3: c.2015C > T (p.Ser672Leu). These findings are consistent with the genetic diagnosis of autosomal dominant primary aldosteronism, seizures, and neurological abnormalities. This variant was found in the heterozygous status in the patient, her father, and her affected sister. Conclusion: This case report will help to determine the key clinical features of this syndrome, which exhibits variable clinical presentations.

Inherited deficiency of stress granule ZNFX1 in patients with monocytosis and mycobacterial disease.

Human inborn errors of IFN-γ underlie mycobacterial disease, due to insufficient IFN-γ production by lymphoid cells, impaired myeloid cell responses to this cytokine, or both. We report four patients from two unrelated kindreds with intermittent monocytosis and mycobacterial disease, including bacillus Calmette-Guérin-osis and disseminated tuberculosis, and without any known inborn error of IFN-γ. The patients are homozygous for ZNFX1 variants (p.S959* and p.E1606Rfs*10) predicted to be loss of function (pLOF). There are no subjects homozygous for pLOF variants in public databases. ZNFX1 is a conserved and broadly expressed helicase, but its biology remains largely unknown. It is thought to act as a viral double-stranded RNA sensor in mice, but these patients do not suffer from severe viral illnesses. We analyze its subcellular localization upon overexpression in A549 and HeLa cell lines and upon stimulation of THP1 and fibroblastic cell lines. We find that this cytoplasmic protein can be recruited to or even induce stress granules. The endogenous ZNFX1 protein in cell lines of the patient homozygous for the p.E1606Rfs*10 variant is truncated, whereas ZNFX1 expression is abolished in cell lines from the patients with the p.S959* variant. Lymphocyte subsets are present at normal frequencies in these patients and produce IFN-γ normally. The hematopoietic and nonhematopoietic cells of the patients tested respond normally to IFN-γ. Our results indicate that human ZNFX1 is associated with stress granules and essential for both monocyte homeostasis and protective immunity to mycobacteria.

Tetrasomy 18p: case report and review of literature.

Tetrasomy 18p syndrome (Online Mendelian Inheritance in Man 614290) is a very rare chromosomal disorder that is caused by the presence of isochromosome 18p, which is a supernumerary marker composed of two copies of the p arm of chromosome 18. Most tetrasomy 18p cases are de novo cases; however, familial cases have also been reported. It is characterized mainly by developmental delays, cognitive impairment, hypotonia, typical dysmorphic features, and other anomalies. Herein, we report de novo tetrasomy 18p in a 9-month-old boy with dysmorphic features, microcephaly, growth delay, hypotonia, and cerebellar and renal malformations. We compared our case with previously reported ones in the literature. Clinicians should consider tetrasomy 18p in any individual with dysmorphic features and cardiac, skeletal, and renal abnormalities. To the best of our knowledge, we report for the first time an association of this syndrome with partial agenesis of cerebellar vermis.

Prevalence of diabetes mellitus and its relation with obesity in Turaif (Saudi Arabia) in 2017.

BACKGROUND: The significant increase in the prevalence of obesity over past decades caused the concomitant rise in the incidence of glucose intolerance and diabetes. OBJECTIVE: To determine the prevalence of diabetes among Saudi nationals in Turaif, Kingdom of Saudi Arabia and to examine the association between diabetes and obesity in the studied population. METHODS: This study was conducted during the period from May 01 to May 31, 2017. Data was collected from 402 individuals aged between 6-63 years via a predesigned questionnaire covering medical history of diabetes, age and sex. Body weight and height was measured to calculate BMI. Data were analyzed by SPSS version 15, using descriptive statistics and Chi-Square test. RESULTS: Mean age (± SD) was 23.27 (±13.509) years, male to female ratio was 38.1% to 61.9%. The total prevalence of DM among the studied population was 4.5%, pre-diabetic cases were 7.5%. There is significant effect of age, sex and BMI on the occurrence of diabetes among the studied population (p<0.05). CONCLUSIONS: Awareness campaigns and prevention programs about diabetes should be instituted and control strategies should be implemented. There is a need for a diabetes screening and management programs, focusing on access to health care in the city.

Epilepsy as a health problem among school children in Turaif, Northern Saudi Arabia, 2017.

BACKGROUND: Epilepsy is the most common serious neurological disorder and is one of the world's most prevalent non-communicable diseases. There are no recently published data on the prevalence of epilepsy in school children in Northern Saudi Arabia. OBJECTIVE: This study was conducted to determine the prevalence of epilepsy and to show some of its risk factors in school children and adolescents (6-18 years) in Turaif city, Northern Saudi Arabia. METHODS: This, population-based, cross-sectional study was conducted in Turaif city, over a 6-month period, from July 2016 to January 2017. It included pupils aged 6 to18 years in all primary, preparatory and secondary schools in Turaif city. Multi-stage sampling was employed. A designated structured questionnaire was completed for each patient and included the patient's history, clinical examination, investigations and medications. Data were analyzed by SPSS version 16, using Chi-Squared test and descriptive statistics. RESULTS: Out of 1,230 children, 66 (5.5%) had epilepsy; 68.2% of them were males and 31.8% females (p=0.000). Consanguinity between parents plays a significant role where 59.1% of cases had parents who were cousins (p=0.000). Family history also had a significant effect as 68.2% of cases had epilepsy cases in their families (p=0.000). CONCLUSION: Epilepsy prevalence among school children (6-18 years) in Turaif city is higher in males than females. Consanguinity and positive family history are important factors. Decision makers must take effective steps to limit the causes and risk factors of the problem.