Corrado Romano

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Verified

Corrado verified their affiliation via an institutional email.

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• MD
• Associate Professor of Medical Genetics at University of Catania

Copy number variants (CNVs) are associated with many neurocognitive disorders; however, these events are typically large, and the underlying causative genes are unclear. We created an expanded CNV morbidity map from 29,085 children with developmental delay in comparison to 19,584 healthy controls, identifying 70 significant CNVs. We resequenced 26...

Parents of autistic children and autism support groups often report that autistic episodes are exacerbated when the children eat certain foodstuffs such as dairy products, chocolates, wheat, corn sugar, apples, and bananas. The hypothesis that autistic behavior might be related to metabolic dysfunctions has led us to investigate in a group of "low...

Down's syndrome (DS) is the most frequent genetic cause of Alzheimer-type dementia. Its metabolic phenotype involves an increased trans-sulphuration of homocysteine. The aim of the present study was to investigate the influence of homocysteinaemia (t-Hcys), folate, vitamin B(12), and related polymorphisms on intelligence quotient (IQ) in DS. The IQ...

This study describes two siblings from consanguineous parents who exhibit intellectual disability, microcephaly, photosensitivity, bilateral sensorineural hearing loss, numerous freckles, and other clinical features that suggest a potential disruption of the nucleotide excision repair (NER) pathway. Whole exome sequencing (WES) identified a novel h...

The loss of one of the two copies of the 9 bp tandem repeat sequence (CCCCCTCTA) located in the small non-coding region between the cytochrome oxidase II (COII) and the lysine tRNA genes in human mtDNA has been reported to be polymorphic in Asian, Oceanian and Sub-Saharan African populations, but it has rarely been observed in Europe. In this study...

Variable expressivity of disease-associated variants implies a role for secondary variants that modify clinical features. We assessed the effects of modifier variants towards clinical outcomes of 2,252 individuals with primary variants. Among 132 families with the 16p12.1 deletion, distinct rare and common variant classes conferred risk for specifi...

ASD is a complex condition primarily rooted in genetics, although influenced by environmental, prenatal, and perinatal risk factors, ultimately leading to genetic and epigenetic alterations. These mechanisms may manifest as inflammatory, oxidative stress, hypoxic, or ischemic damage. To elucidate potential variances in gene expression in ASD, a tra...

Almost all individuals with Down’s syndrome (DS) show the characteristic neuropathological features of Alzheimer’s disease (AD) by the age of 40, yet not every individual with DS experiences symptoms of AD later in life. Similar to neurotypical developing subjects, AD in people with DS lasts for a long preclinical phase in which biomarkers follow a...

Pre-mRNA splicing is a highly coordinated process. While its dysregulation has been linked to neurological deficits, our understanding of the underlying molecular and cellular mechanisms remains limited. We implicated pathogenic variants in U2AF2 and PRPF19, encoding spliceosome subunits in neurodevelopmental disorders (NDDs), by identifying 46 unr...

Gerstmann Sträussler Scheinker (GSS) is an inherited, invariably fatal prion disease. Like other human prion diseases, GSS is caused by missense mutations in the prion protein (PrP) gene (PRNP), and by the formation and overtime accumulation of the misfolded, pathogenic scrapie PrP (PrPSc). The first mutation identified in the PRNP gene, and the on...

Phosphoinositides (PIs) are membrane phospholipids produced through the local activity of PI kinases and phosphatases that selectively add or remove phosphate groups from the inositol head group. PIs control membrane composition and play key roles in many cellular processes including actin dynamics, endosomal trafficking, autophagy, and nuclear fun...

We examined more than 38,000 spouse pairs from four neurodevelopmental disease cohorts and the UK Biobank to identify phenotypic and genetic patterns in parents associated with neurodevelopmental disease risk in children. We identified correlations between six phenotypes in parents and children, including correlations of clinical diagnoses such as...

Background: Individuals with the 2p15p16.1 microdeletion syndrome share a complex phenotype including neurodevelopmental delay, brain malformations, microcephaly, and autistic behavior. The analysis of the shortest region of overlap (SRO) between deletions in ~ 40 patients has led to the identification of two critical regions and four strongly can...

Mitochondrial tRNASer(UCN) is considered a hot-spot for non-syndromic and aminoglycoside-induced hearing loss. However, many patients have been described with more extensive neurological diseases, mainly including epilepsy, myoclonus, ataxia, and myopathy. We describe a novel homoplasmic m.7484A>G mutation in the tRNASer(UCN) gene affecting the thi...

Background: Prader-Willi syndrome (PWS) is a rare and complex genetic disease, with numerous implications on metabolic, endocrine, neuropsychomotor systems, and with behavioural and intellectual disorders. Rare disease patient registries are important scientific tools (1) to collect clinical and epidemiologic data, (2) to assess the clinical manag...

Background Autism spectrum disorders (ASD) are neurodevelopmental disorders, with heterogeneous etiology, characterized by deficiencies in social interaction, communication, and by repetitive and stereotyped behaviors. Mitochondrial encephalomyopathies are inherited disorders of oxidative metabolism, with a wide clinical, biochemical and genetic he...

Loss-of-function variants in CHAMP1 were recently described as cause of a neurodevelopmental disorder characterized by intellectual disability (ID), autism, and distinctive facial characteristics. By exome sequencing (ES), we identified a truncating variant in CHAMP1, c.1858A > T (p.Lys620*), in a patient who exhibited a similar phenotype of severe...

The authors report on a boy with dyslexia and attention deficit hyperactivity disorder. A protocol of standardized tests assessed the neuroadaptive profile, allowing deep neuropsychiatric phenotyping. In addition to the diagnosis of dyslexia and attention deficit hyperactivity disorder, such methodology led to endeavor cognitive, adaptive, and acad...

Background Prader-Willi syndrome (PWS) is a rare and complex genetic disease, with numerous implications on metabolic, endocrine, neuropsychomotor systems, and with behavioural and intellectual disorders. Rare disease patient registries are important scientific tools i) to collect clinical and epidemiologic data, ii) to assess the clinical manageme...

Variants in RAC3, encoding a small GTPase RAC3 which is critical for the regulation of actin cytoskeleton and intracellular signal transduction, are associated with a rare neurodevelopmental disorder with structural brain anomalies and facial dysmorphism. We investigated a cohort of 10 unrelated participants presenting with global psychomotor delay...

Interstitial deletions of the long arm of chromosome 12 are rare, with a dozen patients carrying a deletion in 12q21 being reported. Recently a critical region (CR) has been delimited and could be responsible for the more commonly described clinical features, such as developmental delay/intellectual disability, congenital genitourinary and brain ma...

Previous research yielded conflicting results on the association between cigarette smoking and risk of SARS-CoV-2 infection. Since the prevalence of smoking is high globally, the study of its impact on COVID-19 pandemic may have considerable implications for public health. This study is the first to investigate the association between the SARS-CoV-...

This editorial summarizes the main information leading to a Special Issue on intellectual disability [...].

Background: Prostate cancer (PCa) is one of the leading causes of death in Western countries. Environmental and genetic factors play a pivotal role in PCa etiology. Timely identification of the genetic causes is useful for an early diagnosis. Parkinson's disease (PD) is the most frequent neurodegenerative movement disorder; it is associated with t...

Down syndrome (DS) is defined by the presence of a third copy of chromosome 21. Several comorbidities can be found in these patients, such as intellectual disability (ID), muscle weakness, hypotonia, congenital heart disease, and autoimmune diseases. The molecular mechanisms playing a role in the development of such comorbidities are still unclear....

Background After the global spread of SARS-CoV-2, research has highlighted several aspects of the pandemic, focusing on clinical features and risk factors associated with infection and disease severity. However, emerging results on the role of smoking in SARS-CoV-2 infection susceptibility or COVID-19 outcomes are conflicting, and their robustness...

BACKGROUND After the global spread of SARS-CoV-2, research has highlighted several aspects of the pandemic, focusing on clinical features and risk factors associated with infection and disease severity. However, emerging results on the role of smoking in SARS-CoV-2 infection susceptibility or COVID-19 outcomes are conflicting, and their robustness...

Chromosome 21 trisomy or Down syndrome (DS) is the most common genetic cause of intellectual disability (ID). DS is also associated with hypotonia, muscle weakness, autoimmune diseases, and congenital heart disease. C–C chemokine receptor type 3 (CCR3) plays a role in inflammatory, autoimmune, and neuronal migration mechanisms. The present study ai...

We report the second case, to the best of our knowledge, of a mother with Prader–Willi syndrome (PWS) who gave birth to a daughter with Angelman syndrome (AS). The menarche occurred when she was 16, and the following menstrual cycles were irregular, but she never took sexual hormone replacement therapy. At the age of 26, our patient with PWS became...

After the global spread of severe acute respiratory syndrome coronavirus 2 (SARS−CoV−2), research has highlighted several aspects of the pandemic, focusing on clinical features and risk factors associated with infection and disease severity. However, emerging results on the role of smoking in SARS−CoV−2 infection susceptibility or COVID−19 outcomes...

To date only five patients with 8p23.2-pter microdeletions manifesting a mild-to-moderate cognitive impairment and/or developmental delay, dysmorphisms and neurobehavioral issues were reported. The smallest microdeletion described by Wu in 2010 suggested a critical region (CR) of 2.1 Mb including several genes, out of which FBXO25, DLGAP2, CLN8, AR...

Background With the increasing number of genomic sequencing studies, hundreds of genes have been implicated in neurodevelopmental disorders (NDDs). The rate of gene discovery far outpaces our understanding of genotype–phenotype correlations, with clinical characterization remaining a bottleneck for understanding NDDs. Most disease-associated Mendel...

Introduction Parkinson's disease (PD) is a common adult-onset neurodegenerative disorder caused by a progressive loss of dopaminergic neurons due to the accumulation of α-synuclein in the substantia nigra. Mitochondria are known to play a key role in cell respiratory function and bioenergetics. Indeed, mitochondrial dysfunction causes an insufficie...

Prostate cancer (PCa) is one of the leading causes of death in Western countries. Environmental and genetic factors play a pivotal role in PCa etiology. Timely identification of the genetic causes is useful for an early diagnosis. Parkinson’s disease (PD) is the most frequent neurodegenerative movement disorder; it is associated with the presence o...

Purpose: The etiology of azoospermia in patients with Klinefelter syndrome (KS) is still unknown. The protein codified by the G protein-couple receptor 56 (GPR56) belongs to the adhesion family of G protein-coupled receptors (GPRs). Its mutations are involved in the pathogenesis of intellectual disability and, according to animal studies, infertil...

Most genes associated with neurodevelopmental disorders (NDDs) were identified with an excess of de novo mutations (DNMs) but the significance in case–control mutation burden analysis is unestablished. Here, we sequence 63 genes in 16,294 NDD cases and an additional 62 genes in 6,211 NDD cases. By combining these with published data, we assess a to...

An amendment to this paper has been published and can be accessed via a link at the top of the paper.

Biallelic loss of function of TELO2 gene cause a severe syndromic disease mainly characterized by global developmental delay with poor motor and language acquisitions, microcephaly, short stature, minor facial and limbs anomalies, sleep disorder, spasticity, and balance impairment up to ataxia. TELO2-related syndrome, also known as You-Hoover-Fong...

Klinefelter syndrome (KS) is the most common sex chromosome disorder in men. It is characterized by germ cell loss and other variable clinical features, including autoimmunity. The sex-determining region of Y (SRY)-box 13 (Sox13) gene is expressed in mouse spermatogonia. In addition, it has been identified as islet cell autoantigen 12 (ICA12), whic...

Introduction Cri-du-Chat Syndrome (CdCS) is a genetic condition due to deletions showing different breakpoints encompassing a critical region on the short arm of chromosome 5, located between p15.2 and p15.3, first defined by Niebuhr in 1978. The classic phenotype includes a characteristic cry, peculiar facies, microcephaly, growth retardation, hyp...

Trisomy 21, also known as Down Syndrome (DS), is the most common chromosome abnormality and causes intellectual disability. Long non-coding RNA (lncRNA) growth arrest-specific 5 (GAS5), whose differential expression has recently been reported in patients with Klinefelter syndrome, has been addressed to play a role in the development of inflammatory...

Trisomy 21 or Down syndrome (DS) is the most frequent genetic etiology of intellectual disability in humans. MDM2 gene expression has a potential role as a risk factor for human aneuploidy. -410T-G (rs2279744) functional polymorphism in MDM2 gene impacts on the mechanisms of chromosomal non-disjunction. We analyzed, within a case–control study, suc...

Down syndrome (DS) is characterized by trisomy of chromosome 21 and peculiar phenotype. Humanin (HN) is a mitochondrial short 24-residue polypeptide whit anti-apoptotic and neuroprotective effects. In this study we evaluated HN protein expression and HN mRNA levels in cultured fibroblasts from DS patients and normal controls. Our results obtained b...

Down syndrome (DS) is the most common genetic cause of intellectual disability, resulting from lack of disjunction of sister chromatids of human chromosome 21 or not partial disjunction of chromosome 21 (Hsa21), usually during maternal meiosis. The expression of genes in chromosome 21 is very complex and many other genes in other chromosomes can pl...

Postsynaptic density (PSD) proteins have been implicated in the pathophysiology of neurodevelopmental and psychiatric disorders. Here, we present detailed clinical and genetic data for 20 patients with likely gene-disrupting mutations in TANC2—whose protein product interacts with multiple PSD proteins. Pediatric patients with disruptive mutations p...

RNA binding proteins are key players in posttranscriptional regulation and have been implicated in neurodevelopmental and neuropsychiatric disorders. Here, we report a significant burden of heterozygous, likely gene-disrupting variants in CSDE1 (encoding a highly constrained RNA binding protein) among patients with autism and related neurodevelopme...

The clinical utility of computational phenotyping for both genetic and rare diseases is increasingly appreciated; however, its true potential is yet to be fully realized. Alongside the growing clinical and research availability of sequencing technologies, precise deep and scalable phenotyping is required to serve unmet need in genetic and rare dise...

Developmental and epileptic encephalopathies (DEEs) are genetically heterogenous conditions, often characterized by early onset, EEG interictal epileptiform abnormalities, polymorphous and drug-resistant seizures, and neurodevelopmental impairments. In this study, we investigated the genetic defects in two siblings who presented with severe DEE, mi...

Determining pathogenicity of genomic variation identified by next-generation sequencing techniques can be supported by recurrent disruptive variants in the same gene in phenotypically similar individuals. However, interpretation of novel variants in a specific gene in individuals with mild–moderate intellectual disability (ID) without recognizable...

In recent years, chromosomal microarray analysis has permitted the discovery of rearrangements underlying several neurodevelopmental disorders and still represents the first diagnostic test for unexplained neurodevelopmental disabilities. Here we report a family of consanguineous parents showing psychiatric disorders and their two sons both affecte...

Background Klinefelter syndrome (KS) is characterized by the presence of at least one supernumerary X chromosome. KS typical symptoms include tall stature, gynecomastia, hypogonadism and azoospermia. KS patients show a higher risk of developing metabolic and cardiovascular diseases, inflammatory and autoimmune disorders, osteoporosis and cancer. Lo...

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 s...

Purpose To assess the contribution of rare variants in the genetic background towards variability of neurodevelopmental phenotypes in individuals with rare copy-number variants (CNVs) and gene-disruptive mutations. Methods We analyzed quantitative clinical information, exome-sequencing, and microarray data from 757 probands and 233 parents and sib...

Objective: Cut homeodomain transcription factor CUX2 plays an important role in dendrite branching, spine development, and synapse formation in layer II‐III neurons of the cerebral cortex. We identify a recurrent de novo CUX2 p.Glu590Lys as a novel genetic cause for developmental and epileptic encephalopathy (DEE). Methods: The de novo p.Glu590Lys...

N-alpha-acetylation is a common co-translational protein modification that is essential for normal cell function in humans. We previously identified the genetic basis of an X-linked infantile lethal Mendelian disorder involving a c.109T>C (p.Ser37Pro) missense variant in NAA10, which encodes the catalytic subunit of the N-terminal acetyltransferase...

Background In genome-wide screening studies for de novo mutations underlying autism and intellectual disability, mutations in the ADNP gene are consistently reported amongst the most frequent. ADNP mutations have been identified in children with autism spectrum disorder co-morbid with intellectual disability, facial features and deficits in multipl...

Objectives: Klinefelter syndrome (KS) is one of the most common sex-chromosome disorders as it affects up to 1 in every 600-1000 newborn males. Men with KS carry one extra X chromosome and they usually present a 47,XXY karyotype, but less frequent variants have also been reported in literature. KS typical symptoms include tall stature, gynecomastia...

Genotype-first combined with reverse phenotyping has shown to be a powerful tool in human genetics, especially in the era of next generation sequencing. This combines the identification of individuals with mutations in the same gene and linking these to consistent (endo)phenotypes to establish disease causality. We have performed a MIP (molecular i...

Individuals with Down syndrome are at increased risk of developing Alzheimer's disease due to increase gene dosage resulting from chromosome 21 triplication. Although virtually all adults with Down syndrome will exhibit the major neuropathological hallmarks that define Alzheimer's disease, not all of them will develop the clinical symptoms associat...

Although de novo missense mutations have been predicted to account for more cases of autism than gene-truncating mutations, most research has focused on the latter. We identified the properties of de novo missense mutations in patients with neurodevelopmental disorders (NDDs) and highlight 35 genes with excess missense mutations. Additionally, 40 a...

The authors examine what's meant as facies in medicine. After an introduction to the word's understanding, they move on listing some dermatological conditions associated to peculiar facies in the child. Starting from atopic dermatitis, the authors develop an algorithm including Genodermatoses, Neurocutaneous Disorders, and Multiple Congenital Anoma...

Gene-disruptive mutations contribute to the biology of neurodevelopmental disorders (NDDs), but most of the related pathogenic genes are not known. We sequenced 208 candidate genes from >11,730 cases and >2,867 controls. We identified 91 genes, including 38 new NDD genes, with an excess of de novo mutations or private disruptive mutations in 5.7% o...

Background: A functional polymorphism in the methylenetetrahydrofolate reductase (MTHFR) gene, namely C677T (rs1801133), results in increased Hcy levels and has been associated with risk of late-onset Alzheimer’s disease (LOAD). Many investigators reported association between rs1801133 and LOAD risk in Asian populations and in carriers of the apoli...

Objective: Trisomy 21 is the most frequent genetic cause of intellectual disability. TP53 gene down-regulation triggers chromosomal instability. A TP53 gene polymorphism c.215G > C (rs1042522) is associated with accumulation of aneuploid cells. We analyzed the TP53 c.215G > C (rs1042522) polymorphism in Sicilian mothers of subjects with Down Syndro...

Neurofibromatosis type 1 (NF1) is caused by mutations of the NF1 gene and is one of the most common human autosomal dominant disorders. The patient shows different signs on the skin and other organs from early childhood. The best known are six or more café au lait spots, axillary or inguinal freckling, increased risk of developing benign nerve shea...

Introduction: Given that Alzheimer's pathology develops silently over decades in Down syndrome (DS), prognostic biomarkers of dementia are a major need. Methods: We investigated the plasma levels of Aβ, proNGF, tPA, neuroserpin, metallo-proteases and inflammatory molecules in 31 individuals with DS (with and without dementia) and in 31 healthy c...

Objective: Women with Down's syndrome (DS) experience menopause earlier than healthy women and are twice as likely to undergo premature ovarian insufficiency. Menopause accelerates cognitive decline and is associated with a twofold increased mortality risk in DS women. Nonetheless, no previous studies investigated the ovarian reserve in this popul...

Down syndrome is characterized by dysmorphic features, mental retardation and problems of immune deficiency. Chronic infection by Epstein–Barr virus is frequently present in subjects with Down syndrome. Ksp37 gene is commonly expressed by NK, CD8+ T, γδ T and CD4+ T cells; these data suggest that Ksp37 have cytotoxic properties. An increase of Ksp3...

Intellectual disability (ID) and autism spectrum disorders (ASD) are genetically heterogeneous, and a significant number of genes have been associated with both conditions. A few mutations in POGZ have been reported in recent exome studies; however, these studies do not provide detailed clinical information. We collected the clinical and molecular...

Several nuclear genes have been found to be linked to ichthyosis, and Next Generation Sequencing approach on panels of targeted genes has turned out to be particularly useful in analyzing diseases characterized by significant genetic and phenotypic heterogeneity. We developed a panel of 26 genes to be screened with the Ion Personal Genome Machine (...