Roles of Type 10 17β-Hydroxysteroid Dehydrogenase in Health and Disease.

Type 10 17β-hydroxysteroid dehydrogenase (17β-HSD10) is the gene product. It plays an appreciable part in the carcinogenesis and pathogenesis of neurodegeneration, such as Alzheimer's disease and infantile neurodegeneration. This mitochondrial, homo-tetrameric protein is a central hub in various metabolic pathways, e.

Prediction of amyloid and tau brain deposition and cognitive decline in people with Down syndrome using plasma biomarkers: a longitudinal cohort study.

Background: Plasma biomarkers associated with Alzheimer's disease could improve prognostic assessment for people with Down syndrome in both clinical practice and research settings. We aimed to identify the plasma biomarkers that most accurately predict longitudinal changes in Alzheimer's disease-related pathology and cognitive functioning in individuals with Down syndrome.

Methods: This longitudinal cohort study included data from 258 adults (aged ≥25 years) with Down syndrome who were followed up prospectively every 16 months as part of the longitudinal Alzheimer's Biomarker Consortium-Down Syndrome study (recruited from seven university sites in the USA and UK between July 13, 2016, and Jan 15, 2019).

Addressing the Diagnostic Odyssey for Adults With Neurodevelopmental Disabilities: Case Study of an Individual With Mandibulofacial Dysostosis With Microcephaly.

Whole exome sequencing (WES) has been widely used in the pediatric setting to increase diagnostic yield, provide treatment options, and to estimate reoccurrence risks. However, there is limited knowledge regarding the utility of this technology in adults with neurodevelopmental disabilities. We present a 23-year-old male diagnosed with autism spectrum disorder, intellectual disability, cleft palate, micrognathia, microcephaly, bifid uvula, conductive hearing impairment, and hypotonia.

The Alzheimer's Biomarker Consortium-Down Syndrome (ABC-DS): A 10-year report.

Introduction: Virtually all adults with Down syndrome (DS) will accumulate the neuropathologies associated with Alzheimer's disease (AD) by age 40, with the majority having a clinical dementia diagnosis by their middle 50s.

Methods: This paper complements a 2020 publication describing the Alzheimer's Biomarker Consortium-Down Syndrome (ABC-DS) methodology by highlighting protocol changes since initial funding in 2015. It describes available clinical, neuropsychological, neuroimaging, and biofluid data and bio-specimen repository.

Sex Differences in Natural History and Health Outcomes Among Individuals With Tic Disorders.

Objectives: To analyze sex differences in outcomes in Tourette syndrome (TS) and Persistent Motor or Vocal tic disorders (PMVT) in the Tourette Association of America International Consortium for Genetics (TAAICG) dataset.

Methods: The relationship between sex and clinical measures was explored in 2,403 participants (N = 2,109 with TS; N = 294 with PMVT) from the TAAICG dataset using generalized estimating equation regression models, and adjusted for age and family relationships.

Results: Female (vs male) participants with TS (25.

DNA-binding affinity and specificity determine the phenotypic diversity in BCL11B-related disorders.

BCL11B is a Cys2-His2 zinc-finger (C2H2-ZnF) domain-containing, DNA-binding, transcription factor with established roles in the development of various organs and tissues, primarily the immune and nervous systems. BCL11B germline variants have been associated with a variety of developmental syndromes. However, genotype-phenotype correlations along with pathophysiologic mechanisms of selected variants mostly remain elusive.

Assessment of Adaptive Functioning and the Impact of Seizures in KBG Syndrome.

This study aimed to examine the adaptive functioning status and the impact of epileptic seizures on neurocognitive outcomes in KBG syndrome, a rare genetic neurodevelopmental disorder characterized by pathogenic variants in ANKRD11. A single clinician interviewed individuals and families with genetically confirmed cases of KBG syndrome. Trained professionals also conducted assessments using the Vineland-3 Adaptive Behavior Scales.

Involvement of Type 10 17β-Hydroxysteroid Dehydrogenase in the Pathogenesis of Infantile Neurodegeneration and Alzheimer's Disease.

Type 10 17β-hydroxysteroid dehydrogenase (17β-HSD10) is the gene product playing an appreciable role in cognitive functions. It is the main hub of exercise-upregulated mitochondrial proteins and is involved in a variety of metabolic pathways including neurosteroid metabolism to regulate allopregnanolone homeostasis. Deacetylation of 17β-HSD10 by sirtuins helps regulate its catalytic activities.

Ocular manifestations in a cohort of 43 patients with KBG syndrome.

Ophthalmological conditions are underreported in patients with KBG syndrome, which is classically described as presenting with dental, developmental, intellectual, skeletal, and craniofacial abnormalities. This study analyzed the prevalence of four ophthalmological conditions (strabismus, astigmatism, myopia, hyperopia) in 43 patients with KBG syndrome carrying variants in ANKRD11 or deletions in 16q24.3 and compared it to the literature.

-associated spinocerebellar ataxia with craniofacial features-additional evidence for germline mosaicism.

Inositol 1,4,5-triphosphate receptor type 1 () is an endoplasmic reticulum-bound intracellular inositol triphosphate receptor involved in the regulation of intracellular calcium. Pathogenic variants in are associated with spinocerebellar ataxia (SCA) types 15/16 and 29 and have recently been implicated in a facial microsomia syndrome. In this report, we present a family with three affected individuals found to have a heterozygous missense c.

Insight and Recommendations for Fragile X-Premutation-Associated Conditions from the Fifth International Conference on Premutation.

The premutation of the fragile X messenger ribonucleoprotein 1 () gene is characterized by an expansion of the CGG trinucleotide repeats (55 to 200 CGGs) in the 5' untranslated region and increased levels of mRNA. Molecular mechanisms leading to fragile X-premutation-associated conditions (FXPAC) include cotranscriptional R-loop formations, mRNA toxicity through both RNA gelation into nuclear foci and sequestration of various CGG-repeat-binding proteins, and the repeat-associated non-AUG (RAN)-initiated translation of potentially toxic proteins. Such molecular mechanisms contribute to subsequent consequences, including mitochondrial dysfunction and neuronal death.

Predicting mental and psychomotor delay in very pre-term infants using machine learning.

Background: Very preterm infants are at elevated risk for neurodevelopmental delays. Earlier prediction of delays allows timelier intervention and improved outcomes. Machine learning (ML) was used to predict mental and psychomotor delay at 25 months.

Infantile Neurodegeneration Results from Mutants of 17β-Hydroxysteroid Dehydrogenase Type 10 Rather Than Aβ-Binding Alcohol Dehydrogenase.

Type 10 17β-hydroxysteroid dehydrogenase (17β-HSD10), a homo-tetrameric multifunctional protein with 1044 residues encoded by the gene, is necessary for brain cognitive function. Missense mutations result in infantile neurodegeneration, an inborn error in isoleucine metabolism. A 5-methylcytosine hotspot underlying a 388-T transition leads to the HSD10 (p.

Documentation and prevalence of prenatal and neonatal outcomes in a cohort of individuals with KBG syndrome.

Ankyrin Repeat Domain 11 (ANKRD11) gene mutations are associated with KBG syndrome, a developmental disability that affects multiple organ systems. The function of ANKRD11 in human growth and development is not clear, but gene knockout or mutation are lethal in mice embryos and/or pups. In addition, it plays a vital role in chromatin regulation and transcription.

Efficient Delivery of across the Blood Brain Barrier Using AAVphp Construct in Adult KO Mice Suggests the Feasibility of Gene Therapy for Fragile X Syndrome.

Background Fragile X syndrome (FXS) is the most common inherited cause of intellectual disability and autism. Gene therapy may offer an efficient method to ameliorate the symptoms of this disorder. Methods An AAVphp.

KBG syndrome: videoconferencing and use of artificial intelligence driven facial phenotyping in 25 new patients.

Genetic variants in Ankyrin Repeat Domain 11 (ANKRD11) and deletions in 16q24.3 are known to cause KBG syndrome, a rare syndrome associated with craniofacial, intellectual, and neurobehavioral anomalies. We report 25 unpublished individuals from 22 families with molecularly confirmed diagnoses.

3-Hydroxyacyl-CoA and Alcohol Dehydrogenase Activities of Mitochondrial Type 10 17β-Hydroxysteroid Dehydrogenase in Neurodegeneration Study.

Background: Mitochondrial 17β-hydroxysteroid dehydrogenase type 10 (17β-HSD10) is necessary for brain cognitive function, but its studies were confounded by reports of Aβ-peptide binding alcohol dehydrogenase (ABAD), formerly endoplasmic reticulum-associated Aβ-peptide binding protein (ERAB), for two decades so long as ABAD serves as the alternative term of 17β-HSD10.

Objective: To determine whether those ABAD reports are true or false, even if they were published in prestigious journals.

Methods: 6xHis-tagged 17β-HSD10 was prepared and characterized by well-established experimental procedures.