Substrate specificity controlled by the exit site of human P4-ATPases, revealed by de novo point mutations in neurological disorders.

The maintenance of lipid asymmetry on the plasma membrane is regulated by flippases, such as ATP8A2, ATP11A, and ATP11C, which translocate phosphatidylserine and phosphatidylethanolamine from the outer leaflet to the inner leaflet. We previously identified a patient-derived point mutation (Q84E) in ATP11A at the phospholipid entry site, which acquired the ability to flip phosphatidylcholine (PtdCho). This mutation led to elevated levels of sphingomyelin (SM) in the outer leaflet of the plasma membrane.

Medication-overuse headache-a review of different treatment strategies.

Medication-overuse headache (MOH) can develop from primary headaches. MOH is usually the result of overuse of symptomatic medications. It is a noteworthy personal and societal burden.

GIGYF1 disruption associates with autism and impaired IGF-1R signaling.

Autism spectrum disorder (ASD) represents a group of neurodevelopmental phenotypes with a strong genetic component. An excess of likely gene-disruptive (LGD) mutations in GIGYF1 was implicated in ASD. Here, we report that GIGYF1 is the second-most mutated gene among known ASD high-confidence risk genes.

Loss of FOCAD, operating via the SKI messenger RNA surveillance pathway, causes a pediatric syndrome with liver cirrhosis.

Cirrhosis is usually a late-onset and life-threatening disease characterized by fibrotic scarring and inflammation that disrupts liver architecture and function. While it is typically the result of alcoholism or hepatitis viral infection in adults, its etiology in infants is much less understood. In this study, we report 14 children from ten unrelated families presenting with a syndromic form of pediatric liver cirrhosis.

MECP2-related conditions in males: A systematic literature review and 8 additional cases.

Objective: To present a cohort of 8 males and perform a systematic review of all published cases with a single copy of MECP2 carrying a pathogenic variant.

Methods: We reviewed medical records of males with a single copy of MECP2 carrying a pathogenic variant. We searched in Medline (Pubmed) and Embase to collect all articles which included well-characterized males with a single copy of MECP2 carrying a pathogenic or likely pathogenic variant in MECP2 (1999-2020).

Additional observation of a de novo pathogenic variant in KCNT2 leading to epileptic encephalopathy with clinical features of frontal lobe epilepsy.

Introduction: KCNT2 was recently recognized as a gene associated with neurodevelopmental disorder and epilepsy.

Case Report: We present an additional observation of a 16-year-old male patient with a novel de novo KCNT2 likely pathogenic variant and review the five previously reported cases of de novo variants in this gene.

Discussion: Whole exome sequencing identified the missense variant c.

ATP6V1B2-related epileptic encephalopathy.

ATP6V1B2 encodes a subunit of the lysosomal transmembrane proton pump necessary for adequate functioning of several acid hydrolases. De novo monoallelic variants of this gene have been associated with two distinct phenotypes: Zimmermann-Laband syndrome 2 (ZLS2), an intellectual deficiency/multiple malformation syndrome, and dominant deafness onychodystrophy (DDOD), a multiple malformation syndrome without cognitive involvement. Epilepsy is not observed in DDOD, is variably present in ZLS2, but is a common feature in Zimmermann-Laband syndrome 1 (ZLS1) (caused by monoallelic pathogenic variants in KCNH1) and Zimmermann-Laband syndrome-like (ZLSL) (associated with KCNK4 variants).

Application of Whole-Exome Sequencing in Detecting Copy Number Variants in Patients with Developmental Delay and/or Multiple Congenital Malformations.

Overcoming challenges for the unambiguous detection of copy number variations is essential to broaden our understanding of the role of genomic variants in the clinical phenotype. With the improvement of software and databases, whole-exome sequencing quickly can become an excellent strategy in the routine diagnosis of patients with a developmental delay and/or multiple congenital malformations. However, even after a detailed analysis of pathogenic single-nucleotide variants and indels in known disease genes, using whole-exome sequencing, some patients with suspected syndromic conditions are left without a conclusive diagnosis.

Heterozygous loss of function of is associated with intellectual deficiency, rolandic epilepsy, and language impairment.

Recognition of a de novo mutation in associated with a neurodevelopmental phenotype reinforces its role in 2q23q24 microdeletion syndrome. Using the proband WES data and the probability of loss-of-function intolerance index (pLi) set at 1.0 (highest intolerance constraint), we could target as the candidate gene in this patient.

De Novo Variants in MAPK8IP3 Cause Intellectual Disability with Variable Brain Anomalies.

Using exome sequencing, we have identified de novo variants in MAPK8IP3 in 13 unrelated individuals presenting with an overlapping phenotype of mild to severe intellectual disability. The de novo variants comprise six missense variants, three of which are recurrent, and three truncating variants. Brain anomalies such as perisylvian polymicrogyria, cerebral or cerebellar atrophy, and hypoplasia of the corpus callosum were consistent among individuals harboring recurrent de novo missense variants.

Isolated Central Nervous System Vasculitis as a Manifestation of Neurosarcoidosis.

A 62-year-old male presented to our clinic with recurrent fever, skin lesions (petechiae), scleral wounds, and hilar adenomegaly. A diagnosis of sarcoidosis was established, which resolved with corticosteroid treatment. After a few months, the patient developed confusion and behavioral changes, with few objective neurological deficits.

Microarray as a new tool to study hypertrophic and keloid scarring.

Unlabelled:  Background. Normal wound healing results from a complex set of reactions between blood cells, skin cells, and biochemical mediators including pro- and anti-inflammatory molecules, growth factors, cytokines, hormones, and vitamins. As this cascade of reactions is ultimately regulated by the coordinated expression and silencing of numerous genes, the gene expression analysis of hypertrophic and keloid scarring (HS and KS, respectively) should provide important information and improve our understanding of HS and KS pathophysiology.