Publications by authors named "Teresa Mattina"

Junctional epidermolysis bullosa (JEB) is a rare genodermatosis characterized by fragility of the skin and mucous membranes due to alterations in the dermal epidermal junction. This condition manifests as mechanically induced bullous lesions that heal with hypertrophic granulation tissue and/or atrophic scars. Here, we report two brothers carrying a homozygous LAMB3 missense variant, p.

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  • The GA4GH Phenopacket Schema, released in 2022 and approved as a standard by ISO, allows the sharing of clinical and genomic data, including phenotypic descriptions and genetic information, to aid in genomic diagnostics.
  • Phenopacket Store Version 0.1.19 offers a collection of 6668 phenopackets linked to various diseases and genes, making it a crucial resource for testing algorithms and software in genomic research.
  • This collection represents the first extensive case-level, standardized phenotypic information sourced from medical literature, supporting advancements in diagnostic genomics and machine learning applications.
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  • - The study examines how secondary genetic variants can influence the clinical features of individuals with primary disease-causing variants, suggesting that these modifiers play a significant role in disease expression.
  • - Specifically focusing on the 16p12.1 deletion, researchers identified various rare and common variants that predisposed individuals to specific developmental issues, such as neurological defects and microcephaly.
  • - By analyzing data from different cohorts, the findings indicate that the effects of primary and secondary variants on phenotype vary depending on the specific primary variant involved, highlighting the need for personalized approaches in treatment.
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We examined more than 97,000 families from four neurodevelopmental disease cohorts and the UK Biobank to identify phenotypic and genetic patterns in parents contributing to neurodevelopmental disease risk in children. We identified within- and cross-disorder correlations between six phenotypes in parents and children, such as obsessive-compulsive disorder (R = 0.32-0.

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Optical genome mapping (OGM), which allows analysis of ultra-high molecular weight (UHMW) DNA molecules, represents a response to the restriction created by short-read next-generation-sequencing, even in cases where the causative variant is a neutral copy-number-variant insensitive to quantitative investigations. This study aimed to provide a molecular diagnosis to a boy with Marfan syndrome (MFS) and intellectual disability (ID) carrying a translocation involving chromosomes 3, 4, and 13 and a 1.7 Mb deletion at the breakpoint of chromosome 3.

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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 obsessive-compulsive disorder (R=0.31-0.

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Phelan-McDermid syndrome (PMS) is an infrequently described syndrome that presents with a disturbed development, neurological and psychiatric characteristics, and sometimes other comorbidities. As part of the development of European medical guidelines we studied the definition, phenotype, genotype-phenotype characteristics, and natural history of the syndrome. The number of confirmed diagnoses of PMS in different European countries was also assessed and it could be concluded that PMS is underdiagnosed.

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Background: Down syndrome (DS) is caused by the presence of an extra copy of full or partial human chromosome 21 (Hsa21). Partial (segmental) trisomy 21 (PT21) is the duplication of only a delimited region of Hsa21 and can be associated or not to DS: the study of PT21 cases is an invaluable model for addressing genotype-phenotype correlation in DS. Previous works reported systematic reanalyses of 132 subjects with PT21 and allowed the identification of a 34-kb highly restricted DS critical region (HR-DSCR) as the minimal region whose duplication is shared by all PT21 subjects diagnosed with DS.

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  • - Esophageal atresia/tracheoesophageal fistula (EA/TEF) is a serious birth defect often linked with other abnormalities, but genetic testing only confirms a diagnosis in a small percentage of cases.
  • - In a study involving 67 patients, only 11 (16%) received a definitive or probable genetic diagnosis, indicating that the reasons behind EA/TEF may be more complex and involve multiple genetic and environmental factors.
  • - The research identified specific genetic variants related to certain genes (like TCF4 and FANCA) that may contribute to the EA/TEF conditions, providing new insights into its development.
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EAST/SeSAME syndrome is a rare disease affecting the Central Nervous System (CNS), inner ear, and kidney. The syndrome is due to loss-of-function mutations in the gene encoding the inward-rectifying potassium channel Kir4.1.

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Oculo-auriculo-vertebral spectrum (OAVS) is a developmental disorder of craniofacial morphogenesis. Its etiology is unclear, but assumed to be complex and heterogeneous, with contribution of both genetic and environmental factors. We assessed the occurrence of copy number variants (CNVs) in a cohort of 19 unrelated OAVS individuals with congenital heart defect.

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Osteopoikilosis (OP) is a rare autosomal dominant sclerosing bone disease, caused by heterozygous mutations in the LEMD3 gene. It is characterised by numerous focal lamellar bone compact deposits in the spongiosa. In this case report, we describe a famliar case of OP and review the literature.

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Purpose: Recent studies have identified suggestive prenatal features of RASopathies (e.g., increased nuchal translucency [NT], cystic hygroma [CH], hydrops, effusions, congenital heart diseases [CHD], polyhydramnios, renal anomalies).

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  • - Oculo-auriculo-vertebral spectrum (OAVS) is a rare disorder linked to abnormal development of certain structures in the body, causing diverse issues like ear and facial deformities, vision problems, and spinal irregularities.
  • - The exact cause of OAVS is largely unknown, but researchers suggest it may arise from a combination of genetic, environmental, and epigenetic factors.
  • - A study analyzing DNA methylation in 41 OAVS patients revealed unique epigenetic patterns and variations that suggest epigenetic mechanisms play a role in the disorder’s development.
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Background: Alport syndrome (ATS) is a hereditary progressive hematuric nephropathy associated with sensorineural deafness and ocular abnormalities, which is caused by mutations in the COL4A5 gene (X-linked ATS) and in two autosomal genes, COL4A4 and COL4A3, responsible of both recessive ATS and, when present in heterozygosity, of a spectrum of phenotypes ranging from isolated hematuria to frank renal disease.

Methods: Retrospective analysis of the clinical and genetic features of 76 patients from 34 unrelated ATS families (11 with mutations in COL4A5, 11 in COL4A3, and 12 in COL4A4) and genotype/phenotype correlation for the COL4A3/COL4A4 heterozygotes (34 patients from 14 families).

Results: Eight (24%) of the 34 heterozygous COL4A3 and COL4A4 carriers developed renal failure at a mean age of 57 years, with a significantly lower risk than hemizygous COL4A5 or double heterozygous COL4A3/COL4A4 carriers (p < 0.

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Wiedemann-Steiner syndrome (WDSTS) is a rare autosomal dominant condition caused by heterozygous loss of function variants in the KMT2A (MLL) gene, encoding a lysine N-methyltransferase that mediates a histone methylation pattern specific for epigenetic transcriptional activation. WDSTS is characterized by a distinctive facial phenotype, hypertrichosis, short stature, developmental delay, intellectual disability, congenital malformations, and skeletal anomalies. Recently, a few patients have been reported having abnormal skeletal development of the cervical spine.

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Purpose: The advancements in the next-generation sequencing (NGS) techniques have allowed for rapid, efficient, and cost-time-effective genetic variant detection. However, in both clinical practice and research setting, sequencing is still often limited to the use of gene panels clinically targeted on the genes underlying the disease of interest.

Methods: We performed a neurogenetic study through an NGS-based custom sequencing gene panel in order to screen 16 genes in 8 patients with different types of degenerative cognitive disorders (Alzheimer's disease, mild cognitive impairment, frontotemporal dementia, and dementia associated with Parkinson's disease).

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  • Autism spectrum disorder (ASD) is linked to changes in genes called copy number variants (CNVs), which can cause differences in physical and mental traits in kids with ASD.
  • In a study with 109 children, researchers found that some had significant genetic changes (C-CNVs), while others had different or no changes (NC-CNVs and W-CNVs).
  • Kids with the more serious genetic changes (C-CNVs) showed worse ASD symptoms and some physical differences, while those with non-causative changes (NC-CNVs) had other behavioral issues but didn’t show many differences in brain health or other conditions.
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Nasu-Hakola disease (NHD) is a rare autosomal recessive disorder characterized by progressive presenile dementia and bone cysts, caused by variants in either or . Despite the well-researched role of TREM2 and TYROBP/DAP12 in immunity, immunological phenotypes have never been reported in NHD patients. We initially diagnosed an Italian patient, using whole exome sequencing, with classical NHD clinical sequelae who additionally showed a decrease in NK cells and autoimmunity features underlined by the presence of autoantibodies.

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Background: Down syndrome (DS) is characterized by the presence of an extra full or partial human chromosome 21 (Hsa21). An invaluable model to define genotype-phenotype correlations in DS is the study of the extremely rare cases of partial (segmental) trisomy 21 (PT21), the duplication of only a delimited region of Hsa21 associated or not to DS. A systematic retrospective reanalysis of 125 PT21 cases described up to 2015 allowed the creation of the most comprehensive PT21 map and the identification of a 34-kb highly restricted DS critical region (HR-DSCR) as the minimal region whose duplication is shared by all PT21 subjects diagnosed with DS.

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Melorheostosis (MEL) is an uncommon, sclerosing disease, characterised by hyperostosis of long bones, resembling the flowing of candle wax. The disease is sporadic and the pathogenesis is still poorly understood. Occasionally, the same family can include individuals with MEL and Osteopoikilosis (OPK), a disease characterised by multiple round foci of increased bone density.

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Hereditary multiple osteochondromas (HMO) is a rare autosomal dominant skeletal disorder, caused by heterozygous variants in either EXT1 or EXT2, which encode proteins involved in the biogenesis of heparan sulphate. Pathogenesis and genotype-phenotype correlations remain poorly understood. We studied 114 HMO families (158 affected individuals) with causative EXT1 or EXT2 variants identified by Sanger sequencing, or multiplex ligation-dependent probe amplification and qPCR.

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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 affected by intellectual disability, ataxia, and behavioral disorder. SNP/CGH array analysis in this family demonstrated in both siblings a biallelic duplication inherited from the heterozygous parents, disrupting the ADGRB3 gene.

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Ets-1 is a member of the Ets family of transcription factors and has critical roles in multiple biological functions. Structural kidney defects occur at an increased frequency in Jacobsen syndrome (OMIM #147791), a rare chromosomal disorder caused by deletions in distal 11q, implicating at least one causal gene in distal 11q. In this study, we define an 8.

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