Psychomotor delay, dysmorphsim and epilepsy with underlying genetic etiology: A case report of first child with a genetically confirmed diagnosis of Angelman Syndrome on a hospital-based setting in Iraq

In this case report we discuss essential issue to be considered with regard to the clinical genetic testing in the epilepsies. The identification of genes that influence risk for the epilepsies has extremely important implications for both research and clinical practice. In a research context, information obtained may lead to the development of new treatments targeted to specific mechanisms, or even to ways of preventing epileptogenesis. In clinical practice, the use of genetic information can either clarify the diagnosis in people already known or suspected to have epilepsy (diagnostic testing), or to predict onset of epilepsy in people at risk of developing epilepsy because of a family history (predictive testing). This 8-year old girl presented because of rapid regression in the cognitive function and had disturbed consciousness which started few weeks before admission. History of delayed milestones, epilepsy, subtle facial dysmorphology, ataxic gait and happy demeanor collectively raised suspicion of genetic/metabolic disorder. Genetic study discovered a deletion involving the maternally derived chromosome 15q11 region and this deletion is associated with Angelman Syndrome

Guillian Barré Syndrome in a sample of Iraqi Children: Seasonal and sex variation

Background: Seasonal variation and gender preponderance have not been adequately studied in Guillain-Barre syndrome (GBS). Objective: This study aims to evaluate the seasonal variation and sex preponderance in children with Guillian Barré Syndrome. Patients and methods: A cross sectional study was carried out by reviewing wards’ registry of all cases with Guillian Barré Syndrome admitted to Children Welfare Teaching Hospital during a 10-year period (1999 - 2008). Age, sex, seasonal distribution, residence and outcome were analysed. Results: Guillian Barré Syndrome was diagnosed in 217 (126 boys, 91 girls) patients and the annual hospital rate of admission was 22.9 /100000 children. There was increase annual incidence from 1999 till 2008 with a drop in 2006, boys: girls ratio was 1.4:1 and boys were older than girls. Clustering of cases was found during January, March, May and November over the 10-year period, 37% of cases occurred during winter and 52.5% of patients were from Baghdad. Conclusion: Guillian Barré Syndrome is more common in boys. Boys were older than girls. Clustering of cases was found during winter season

MED27 Variants Cause Developmental Delay, Dystonia, and Cerebellar Hypoplasia

The Mediator multiprotein complex functions as a regulator of RNA polymerase II-catalyzed gene transcription. In this study, exome sequencing detected biallelic putative disease-causing variants in MED27, encoding Mediator complex subunit 27, in 16 patients from 11 families with a novel neurodevelopmental syndrome. Patient phenotypes are highly homogeneous, including global developmental delay, intellectual disability, axial hypotonia with distal spasticity, dystonic movements, and cerebellar hypoplasia. Seizures and cataracts were noted in severely affected individuals. Identification of multiple patients with biallelic MED27 variants supports the critical role of MED27 in normal human neural development, particularly for the cerebellum. ANN NEUROL 2021Peer reviewe

Biallelic Variants in the Ectonucleotidase ENTPD1 Cause a Complex Neurodevelopmental Disorder with Intellectual Disability, Distinct White Matter Abnormalities, and Spastic Paraplegia

Objective: Human genomics established that pathogenic variation in diverse genes can underlie a single disorder. For example, hereditary spastic paraplegia is associated with >80 genes, with frequently only few affected individuals described for each gene. Herein, we characterize a large cohort of individuals with biallelic variation in ENTPD1, a gene previously linked to spastic paraplegia 64 (Mendelian Inheritance in Man # 615683). Methods: Individuals with biallelic ENTPD1 variants were recruited worldwide. Deep phenotyping and molecular characterization were performed. Results: A total of 27 individuals from 17 unrelated families were studied; additional phenotypic information was collected from published cases. Twelve novel pathogenic ENTPD1 variants are described (NM 001776.6): c.398_399delinsAA; p.(Gly133Glu), c.540del; p.(Thr181Leufs*18), c.640del; p.(Gly216Glufs*75), c.185 T > G; p.(Leu62*), c.1531 T > C; p.(*511Glnext*100), c.967C > T; p.(Gln323*), c.414-2_414-1del, and c.146 A > G; p.(Tyr49Cys) including 4 recurrent variants c.1109 T > A; p.(Leu370*), c.574-6_574-3del, c.770_771del; p.(Gly257Glufs*18), and c.1041del; p.(Ile348Phefs*19). Shared disease traits include childhood onset, progressive spastic paraplegia, intellectual disability (ID), dysarthria, and white matter abnormalities. In vitro assays demonstrate that ENTPD1 expression and function are impaired and that c.574-6_574-3del causes exon skipping. Global metabolomics demonstrate ENTPD1 deficiency leads to impaired nucleotide, lipid, and energy metabolism. Interpretation: The ENTPD1 locus trait consists of childhood disease onset, ID, progressive spastic paraparesis, dysarthria, dysmorphisms, and white matter abnormalities, with some individuals showing neurocognitive regression. Investigation of an allelic series of ENTPD1 (1) expands previously described features of ENTPD1-related neurological disease, (2) highlights the importance of genotype-driven deep phenotyping, (3) documents the need for global collaborative efforts to characterize rare autosomal recessive disease traits, and (4) provides insights into disease trait neurobiology. ANN NEUROL 2022

A homozygous MED11 C-terminal variant causes a lethal neurodegenerative disease

The mediator (MED) multisubunit-complex modulates the activity of the transcriptional machinery, and genetic defects in different MED subunits (17, 20, 27) have been implicated in neurologic diseases. In this study, we identified a recurrent homozygous variant in MED11 (c.325C>T; p.Arg109Ter) in 7 affected individuals from 5 unrelated families