Heterozygosity for loss-of-function variants in LZTR1 is associated with isolated multiple café-au-lait macules.

Purpose: Pathogenic LZTR1 variants cause schwannomatosis and dominant/recessive Noonan syndrome (NS). We aim to establish an association between heterozygous loss-of-function LZTR1 alleles and isolated multiple café-au-lait macules (CaLMs).

Methods: A total of 849 unrelated participants with multiple CaLMs, lacking pathogenic/likely pathogenic NF1 and SPRED1 variants, underwent RASopathy gene panel sequencing.

Impact of the Allergic Therapeutic Adherence in Children with Allergic Rhinitis and ADHD: A Pilot Study.

Background: Allergic rhinitis (AR) is the most common chronic allergic disease in children. Several studies have shown an association between attention deficit hyperactivity disorder (ADHD) and allergies, especially AR. Patients with ADHD usually have poor therapeutic adherence, and untreated AR symptoms may worsen the quality of life of patients.

A Machine Learning Approach to the Diagnosis of Autism Spectrum Disorder and Multi-Systemic Developmental Disorder Based on Retrospective Data and ADOS-2 Score.

Early and accurate diagnosis of autism spectrum disorders (ASD) and tailored therapeutic interventions can improve prognosis. ADOS-2 is a standardized test for ASD diagnosis. However, owing to ASD heterogeneity, the presence of false positives remains a challenge for clinicians.

Cell-free DNA next-generation sequencing liquid biopsy as a new revolutionary approach for arteriovenous malformation.

Objective: Somatic mosaicism of gene is currently recognized as the only established molecular basis of arteriovenous malformations (AVM). However, given the limitations of the current technologies, somatic mutations are detected only in a limited proportion of AVMs and tissue biopsy remains an invasive high risky, sometimes life-threatening, diagnostic procedure. Next-generation sequencing liquid biopsy using cell-free DNA (cfDNA) has emerged as an innovative noninvasive approach for early detection and monitoring of cancer.

Corrigendum: Exome Sequencing in BRCA1-2 Candidate Familias: The Contribution of Other Cancer Susceptibility Genes.

[This corrects the article DOI: 10.3389/fonc.2021.

IQSEC2 disorder: A new disease entity or a Rett spectrum continuum?

IQSEC2 mutations are associated with IQSEC2-related intellectual disability (ID). Phenotypic spectrum has been better defined in the last few years by the increasing number of reported cases although the genotype-phenotype relationship for IQSEC2 remains overall complex. As for IQSEC2-related ID a wide phenotypic diversity has been described in Rett syndrome (RTT).

CDKL5 mutations may mimic Pitt-Hopkins syndrome phenotype.

Genetic conditions comprise a wide spectrum of different phenotypes, rapidly expanding due to new diagnostic methodologies. Patients' facial features and clinical history represent the key elements leading clinicians to the right diagnosis. CDKL5-early onset epilepsy and Pitt-Hopkins syndrome are two well-known genetic conditions, with a defined phenotype sharing some common characteristics like early-onset epilepsy and hyperventilation episodes.

MET somatic activating mutations are responsible for lymphovenous malformation and can be identified using cell-free DNA next generation sequencing liquid biopsy.

Objective: Germline mutations of either the endothelial cell-specific tyrosine kinase receptor TIE2 or the glomulin (GLMN) gene are responsible for rare inherited venous malformations. Both genes affect the hepatocyte growth factor receptor c-Met, inducing vascular smooth muscle cell migration. Germline mutations of hepatocyte growth factor are responsible for lymphatic malformations, leading to lymphedema.

A pilot study of next generation sequencing-liquid biopsy on cell-free DNA as a novel non-invasive diagnostic tool for Klippel-Trenaunay syndrome.

Objectives: Somatic mosaicism of gene is currently recognized as the molecular driver of Klippel-Trenaunay syndrome. However, given the limitation of the current technologies, somatic mutations are detected only in a limited proportion of Klippel-Trenaunay syndrome cases and tissue biopsy remains an invasive high risky, sometimes life-threatening, diagnostic procedure. Next generation sequencing liquid biopsy using cell-free DNA has emerged as an innovative non-invasive approach for early detection and monitoring of cancer.

MEIS2 gene is responsible for intellectual disability, cardiac defects and a distinct facial phenotype.

Myeloid ecotropic insertion site 2 (MEIS2) gene, encoding a homeodomain-containing transcription factor, has been recently related to syndromic intellectual disability with cleft palate and cardiac defects. Here, we present a male patient, aged 10, with cardiac defects, intellectual disability, facial dysmorphisms and gastroesophageal reflux. Whole exome sequencing revealed a novel de novo nonsense mutation in the MEIS2 gene.

Evidence of predisposing epimutation in retinoblastoma.

Retinoblastoma (RB), which represents the most common childhood eye cancer, is caused by biallelic inactivation of RB1 gene. Promoter hypermethylation is quite frequent in RB tissues but conclusive evidence of soma-wide predisposing epimutations is currently scant. Here, 50 patients who tested negative for RB1 germline sequence alterations were screened for aberrant promoter methylation using methylation-specific MLPA.

Rare variants in the genetic background modulate cognitive and developmental phenotypes in individuals carrying disease-associated variants.

Purpose: To assess the contribution of rare variants in the genetic background toward variability of neurodevelopmental phenotypes in individuals with rare copy-number variants (CNVs) and gene-disruptive variants.

Methods: We analyzed quantitative clinical information, exome sequencing, and microarray data from 757 probands and 233 parents and siblings who carry disease-associated variants.

Results: The number of rare likely deleterious variants in functionally intolerant genes ("other hits") correlated with expression of neurodevelopmental phenotypes in probands with 16p12.

[Mitral valve prolapse and parasystolic ventricular tachycardia: an unusual association].

Ventricular arrhythmias are common in patients with mitral valve prolapse. Conversely, parasystolic ventricular tachycardia is an uncommon arrhythmia that can be observed independent of preexisting heart disease. We report the case of an otherwise healthy 42-year-old woman with both mitral valve prolapse and parasystolic ventricular tachycardia.

Recurrent acute myocardial infarction and Kounis syndrome.

Kounis syndrome is the concurrence of acute coronary syndromes with conditions associated with mast cell activation including allergic or hypersensitivity and anaphylactic or anaphylactoid insults. We present a case of recurrent acute myocardial infarction associated with an allergic reaction in an 83-year-old Italian woman.