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Genomic Landscape and Mutational Spectrum of ADAMTS Family Genes in Mendelian Disorders Based on Gene Evidence Review for Variant Interpretation.

ABSTRACT: ADAMTS (a disintegrin and metalloproteinase with thrombospondin motifs) are a family of multidomain extracellular protease enzymes with 19 members. A growing number of ADAMTS family gene variants have been identified in patients with various hereditary diseases. To understand the genomic landscape and mutational spectrum of ADAMTS family genes, we evaluated all reported variants in the ClinVar database and Human Gene Mutation Database (HGMD), as well as recent literature on Mendelian hereditary disorders associated with ADAMTS family genes. Among 1089 variants in 14 genes reported in public databases, 307 variants previously suggested for pathogenicity in Mendelian diseases were comprehensively re-evaluated using the American College of Medical Genetics and Genomics (ACMG) 2015 guideline. A total of eight autosomal recessive genes were annotated as being strongly associated with specific Mendelian diseases, including two recently discovered genes (ADAMTS9 and ADAMTS19) for their causality in congenital diseases (nephronophthisis-related ciliopathy and nonsyndromic heart valve disease, respectively). Clinical symptoms and affected organs were extremely heterogeneous among hereditary diseases caused by ADAMTS family genes, indicating phenotypic heterogeneity despite their structural and functional similarity. ADAMTS6 was suggested as presenting undiscovered pathogenic mutations responsible for novel Mendelian disorders. Our study is the first to highlight the genomic landscape of ADAMTS family genes, providing an appropriate genetic approach for clinical use.

SUBMITTER: Rim JH

PROVIDER: S-EPMC7175297 | biostudies-literature | 2020 Mar

REPOSITORIES: biostudies-literature

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Genomic Landscape and Mutational Spectrum of ADAMTS Family Genes in Mendelian Disorders Based on Gene Evidence Review for Variant Interpretation.

Rim John Hoon JH Choi Yo Jun YJ Gee Heon Yung HY

Biomolecules 20200313 3

ADAMTS (a disintegrin and metalloproteinase with thrombospondin motifs) are a family of multidomain extracellular protease enzymes with 19 members. A growing number of ADAMTS family gene variants have been identified in patients with various hereditary diseases. To understand the genomic landscape and mutational spectrum of ADAMTS family genes, we evaluated all reported variants in the ClinVar database and Human Gene Mutation Database (HGMD), as well as recent literature on Mendelian hereditary ...[more]

PMID: 32183147

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Project description:BACKGROUND:Autism spectrum disorders (ASDs) are characterised by impairments in communication and reciprocal social interaction. These impairments can impact on relationships with family members, augment stress and frustration, and contribute to behaviours that can be described as challenging. Family members of individuals with ASD can experience high rates of carer stress and burden, and poor parental efficacy. While there is evidence to suggest that individuals with ASD and family members derive benefit from psychological interventions designed to reduce stress and mental health morbidity, and enhance coping, most studies to date have targeted the needs of either individuals with ASD, or family members. We wanted to examine whether family (systemic) therapy, aimed at enhancing communication, relationships or coping, is effective for individuals with ASD and their wider family network. OBJECTIVES:To evaluate the clinical effectiveness and acceptability of family therapy as a treatment to enhance communication or coping for individuals with ASD and their family members. If possible, we will also seek to establish the economic costs associated with family therapy for this clinical population. SEARCH METHODS:On 16 January 2017 we searched CENTRAL, MEDLINE, Embase, 10 other databases and three trials registers. We also handsearched reference lists of existing systematic reviews and contacted study authors in the field. SELECTION CRITERIA:Randomised controlled trials (RCTs) and quasi-RCTs investigating the effectiveness of family therapy for young people or adults with ASD or family members, or both, delivered via any modality and for an unspecified duration, compared with either standard care, a wait-list control, or an active intervention such as an alternative type of psychological therapy. DATA COLLECTION AND ANALYSIS:Two authors independently screened each title and abstract and all full-text reports retrieved. To enhance rigour, 25% of these were independently screened by a third author. MAIN RESULTS:The search yielded 4809 records. Of these, we retrieved 37 full-text reports for further scrutiny, which we subsequently excluded as they did not meet the review inclusion criteria, and identified one study awaiting classification. AUTHORS' CONCLUSIONS:Few studies have examined the effectiveness of family therapy for ASD, and none of these are RCTs. Further research studies employing methodologically robust trial designs are needed to establish whether family therapy interventions are clinically beneficial for enhancing communication, strengthening relationships, augmenting coping and reducing mental health morbidity for individuals with ASD and family members.

Dataset Information

Genomic Landscape and Mutational Spectrum of ADAMTS Family Genes in Mendelian Disorders Based on Gene Evidence Review for Variant Interpretation.

Publications

Genomic Landscape and Mutational Spectrum of ADAMTS Family Genes in Mendelian Disorders Based on Gene Evidence Review for Variant Interpretation.

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