ClinPrior: an algorithm for diagnosis and novel gene discovery by network-based prioritization.

Background: Whole-exome sequencing (WES) and whole-genome sequencing (WGS) have become indispensable tools to solve rare Mendelian genetic conditions. Nevertheless, there is still an urgent need for sensitive, fast algorithms to maximise WES/WGS diagnostic yield in rare disease patients. Most tools devoted to this aim take advantage of patient phenotype information for prioritization of genomic data, although are often limited by incomplete gene-phenotype knowledge stored in biomedical databases and a lack of proper benchmarking on real-world patient cohorts.

Translational Diagnostics: An In-House Pipeline to Validate Genetic Variants in Children with Undiagnosed and Rare Diseases.

Diagnosis is essential for the management and treatment of patients with rare diseases. In a group of patients, the genetic study identifies variants of uncertain significance or inconsistent with the phenotype; therefore, it is urgent to develop novel strategies to reach the definitive diagnosis. Herein, we develop the in-house Translational Diagnostics Program (TDP) to validate genetic variants as part of the diagnostic process with the close collaboration of physicians, clinical scientists, and research scientists.

Complete loss of KCNA1 activity causes neonatal epileptic encephalopathy and dyskinesia.

Background: Since 1994, over 50 families affected by the episodic ataxia type 1 disease spectrum have been described with mutations in , encoding the voltage-gated K channel subunit Kv1.1. All of these mutations are either transmitted in an autosomal-dominant mode or found as events.

Right Structural and Functional Reorganization in Four-Year-Old Children with Perinatal Arterial Ischemic Stroke Predict Language Production.

Brain imaging methods have contributed to shed light on the mechanisms of recovery after early brain insult. The assumption that the unaffected right hemisphere can take over language functions after left perinatal stroke is still under debate. Here, we report how patterns of brain structural and functional reorganization were associated with language outcomes in a group of four-year-old children with left perinatal arterial ischemic stroke (PAIS).

Broadening the spectrum of neonatal hemochromatosis.

Neonatal hemochromatosis (NH) has been defined as neonatal liver disorder accompanied by extrahepatic siderosis, and gestational alloimmune liver disease (GALD) is the main cause of NH. We report an atypical case of NH that may have gone underdiagnosed. A male infant was born at term after an uneventful antenatal period.

Language learning and brain reorganization in a 3.5-year-old child with left perinatal stroke revealed using structural and functional connectivity.

Brain imaging methods have contributed to shed light on the possible mechanisms of recovery and cortical reorganization after early brain insult. The idea that a functional left hemisphere is crucial for achieving a normalized pattern of language development after left perinatal stroke is still under debate. We report the case of a 3.

Review and evaluation of the methodological quality of the existing guidelines and recommendations for inherited neurometabolic disorders.

Background: Inherited neurometabolic disorders (iNMDs) represent a group of almost seven hundred rare diseases whose common manifestations are clinical neurologic or cognitive symptoms that can appear at any time, in the first months/years of age or even later in adulthood. Early diagnosis and timely treatments are often pivotal for the favorable course of the disease. Thus, the elaboration of new evidence-based recommendations for iNMD diagnosis and management is increasingly requested by health care professionals and patients, even though the methodological quality of existing guidelines is largely unclear.

X-inactivation of HSD17B10 revealed by cDNA analysis in two female patients with 17β-hydroxysteroid dehydrogenase 10 deficiency.

17β-Hydroxysteroid dehydrogenase 10 (HSD10) is a mitochondrial enzyme involved in the degradation pathway of isoleucine and branched-chain fatty acids. The gene encoding HSD10, HSD17B10, has been reported as one of the few genes that escapes X-inactivation. We previously studied two female patients with HSD10 deficiency, one of them was severely affected and the other presented a mild phenotype.

Study of patients and carriers with 2-methyl-3-hydroxybutyryl-CoA dehydrogenase (MHBD) deficiency: difficulties in the diagnosis.

Objectives: To search for biochemical and molecular markers for the diagnosis of patients and carriers with 2-Methyl-3-hydroxybutyryl-CoA dehydrogenase (MHBD) deficiency.

Design And Methods: Organic acids in urine, MHBD activity in fibroblasts, immunoblotting and molecular studies were performed in seven patients. Seven carriers were also studied.