Silvia Maitz
A5019234351- Genomics and Rare Diseases
- Genomic variations and chromosomal abnormalities
- Genetics and Neurodevelopmental Disorders
- Genetic Syndromes and Imprinting
- Epigenetics and DNA Methylation
- Prenatal Screening and Diagnostics
- Congenital heart defects research
- Genomics and Chromatin Dynamics
- RNA modifications and cancer
- Immunodeficiency and Autoimmune Disorders
- RNA regulation and disease
- Chromatin Remodeling and Cancer
- Cancer-related gene regulation
- Genetic factors in colorectal cancer
- Metabolism and Genetic Disorders
- Liver Diseases and Immunity
- Chromosomal and Genetic Variations
- Connective tissue disorders research
- Drug Transport and Resistance Mechanisms
- Neurofibromatosis and Schwannoma Cases
- Williams Syndrome Research
- Neurogenetic and Muscular Disorders Research
- RNA Research and Splicing
- Congenital Heart Disease Studies
- Cholangiocarcinoma and Gallbladder Cancer Studies
Azienda Ospedaliera San Gerardo
2013-2024
Ente Ospedaliero Cantonale
2023-2024
Fondazione Lanza
2017-2023
Institute of Oncology Research
2023
Washington Center
2022
University of Milano-Bicocca
2010-2020
Fondazione IRCCS Istituto Neurologico Carlo Besta
2020
National Center on Birth Defects and Developmental Disabilities
2009-2019
Universidad Gerardo Barrios
2013
Istituti di Ricovero e Cura a Carattere Scientifico
2010
Overlapping clinical phenotypes and an expanding breadth complexity of genomic associations are a growing challenge in the diagnosis management Mendelian disorders. The functional consequences impacts variation may involve unique, disorder-specific, DNA methylation episignatures. In this study, we describe 19 novel episignature disorders compare findings alongside 38 previously established episignatures for total 57 associated with 65 genetic syndromes. We demonstrate increasing resolution...
With the increasing number of genomic sequencing studies, hundreds genes have been implicated in neurodevelopmental disorders (NDDs). The rate gene discovery far outpaces our understanding genotype-phenotype correlations, with clinical characterization remaining a bottleneck for NDDs. Most disease-associated Mendelian are members families, and we hypothesize that those related molecular function share presentations.We tested hypothesis by considering families multiple an enrichment de novo...
An expanding range of genetic syndromes are characterized by genome-wide disruptions in DNA methylation profiles referred to as episignatures. Episignatures distinct, highly sensitive, and specific biomarkers that have recently been applied clinical diagnosis syndromes. contained within the broader disorder-specific changes, which can share significant overlap among different conditions. In this study, we performed functional genomic assessment comparison overlapping changes related 65 with...
Abstract Variants in RAC3, encoding a small GTPase RAC3 which is critical for the regulation of actin cytoskeleton and intracellular signal transduction, are associated with rare neurodevelopmental disorder structural brain anomalies facial dysmorphism. We investigated cohort 10 unrelated participants presenting global psychomotor delay, hypotonia, behavioural disturbances, stereotyped movements, dysmorphic features, seizures musculoskeletal abnormalities. MRI revealed complex pattern...
Multiple (epi)genetic defects affecting the expression of imprinted genes within 11p15.5 chromosomal region underlie Silver-Russell (SRS) and Beckwith-Wiedemann (BWS) syndromes. The molecular diagnosis these opposite growth disorders requires a multi-approach flowchart to disclose known primary secondary alterations; however, up 20 30 % clinically diagnosed BWS SRS cases remain without diagnosis. complex structure 11p15 with variable CpG methylation low-rate mosaicism may account for missed...
Chromosome 16 is one of the most gene-rich chromosomes our genome, and 10% its sequence consists segmental duplications, which give instability predisposition to rearrangement by recurrent mechanism non-allelic homologous recombination. Microarray technologies have allowed for analysis copy number variations (CNVs) that can contribute risk developing complex diseases. By array comparative genomic hybridization (CGH) screening 1476 patients, we detected 27 cases with CNVs on chromosome 16. We...
Abstract CHD8 has been reported as an autism susceptibility/intellectual disability gene but emerging evidence suggests that it additionally causes overgrowth phenotype. This study reports 27 unrelated patients with pathogenic or likely variants (25 null variants, two missense variants) and a male:female ratio of 21:6 (3.5:1, p < .01). All presented intellectual disability, 85% in the mild moderate range, had height and/or head circumference ≥2 standard deviations above mean, meeting our...
Postzygotic activating PIK3CA variants cause several phenotypes within the PIK3CA-related overgrowth spectrum (PROS). Variant strength, mosaicism level, specific tissue involvement and overlapping disorders are responsible for disease heterogeneity. We explored these factors in 150 novel patients an expanded cohort of 1007 PIK3CA-mutated patients, analysing our new data with previous literature to give a comprehensive picture.We performed ultradeep targeted next-generation sequencing (NGS)...
Noonan syndrome (NS) is a relatively common developmental disorder with pleomorphic phenotype. Mutations causing NS alter genes encoding proteins involved in the RAS-MAPK pathway. We and others identified Casitas B-lineage lymphoma proto-oncogene (CBL), which encodes an E3-ubiquitin ligase acting as tumor suppressor myeloid malignancies, disease gene underlying condition clinically related to NS. Here, we further explored spectrum of germline CBL mutations their associated mutation scanning...
We designate a novel term “isolated lateralized overgrowth” (ILO) for the findings previously described as hemihypertrophy” and hemihyperplasia.” ILO is defined overgrowth in absence of recognized pattern malformations, dysplasia, or morphologic variants. likely genetically heterogeneous. Further study required to determine more underlying genetic etiologies potential associations with currently unrecognized patterns malformation.
We provide data on fetal growth pattern the molecular subtypes of Beckwith-Wiedemann syndrome (BWS): IC1 gain methylation (IC1-GoM), IC2 loss (IC2-LoM), 11p15.5 paternal uniparental disomy (UPD), and CDKN1C mutation. In this observational study, gestational ages neonatal parameters 247 BWS patients were compared by calculating age-corrected standard deviation scores (SDS) proportionality indexes to search for differences among IC1-GoM (n = 21), UPD 87), IC2-LoM 147), mutation 11) patients....
Beckwith-Wiedemann syndrome (BWS) is a rare disorder characterized by overgrowth and predisposition to embryonal tumors. BWS caused various epigenetic and/or genetic alterations that dysregulate the imprinted genes on chromosome region 11p15.5. Molecular analysis required reinforce clinical diagnosis of identify patients with cancer susceptibility. This particularly crucial prenatally because most signs cannot be recognized in utero. We established reliable molecular assay pyrosequencing...
Cornelia de Lange syndrome (CdLS) is a rare genetic condition related to mutation of various cohesion complex genes. Its natural history quite well characterized as regard pediatric age. Relatively little information available regarding the evolution disease in young‐adult In medical literature, only one specific study has been published on this topic. We report our experience 73 Italian CdLS patients (40 males and 33 females) with age range from 15 49 years. Our results confirm previous...
Abstract A whole exome sequencing approach was recently used to detect a CELSR1 truncating variant associated with lymphedema in large pedigree. Since this first report, no other similar associations have been reported the literature. Here, we present genetic results of 95 probands tested using next generation panel that covered all known lymphedema‐associated genes, including . Five out (5.3%) were found carry novel loss‐of‐function variants Family segregation studies possible four five and...
Rett syndrome (RTT) is a neurodevelopmental disorder, affecting 1 in 10,000 girls. Intellectual disability, loss of speech and hand skills with stereotypies, seizures ataxia are recurrent features. Stringent diagnostic criteria distinguish classical Rett, caused by MECP2 pathogenic variant 95% cases, from atypical girls, 40–73% carrying variants, rarely CDKL5 FOXG1 alterations. A large fraction RTT-like patients remain without genetic cause. Next Generation Sequencing (NGS) targeted to...
Pathogenic variants in HNRNPH1 were first reported 2018. The individual, a 13 year old boy with c.616C>T (p.R206W) variant the gene, was noted to have overlapping symptoms those observed HNRNPH2-related X-linked intellectual disability, Bain type (MRXSB), specifically disability and dysmorphic features. While initially proposed represent an autosomal cause of MRXSB, we report additional seven cases which identify phenotypic differences from MRXSB. Patients pathogenic diagnosed via WES...