Topic 137

genetics variant variants autosomal recessive missense mutations exome gene homozygous defects loss heterozygous cause disorder dominant sequencing mutation identified zebrafish candidate pathogenic genetic abnormalities phenotype family families congenital biallelic associated function genes coding mutant novo syndrome developmental functional inherited alleles affected deleterious de mice linked encoding hypoplasia rare protein nonsense chromosome frameshift encodes syndromic null hearing whole consequences etiology neurodevelopmental deafness germline probands cilia cas9 predicted patients component novel affecting crispr phenotypes mouse codon hypotonia lethality deletion delay normal substitution cerebellar deletions unrelated skeletal allele severe individuals homozygosity likely progressive spectrum segregating haploinsufficiency ciliopathies humans histological type hypomorphic characterized splicing

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Novel Loss-of-Function Mutations in COCH Cause Autosomal Recessive Nonsyndromic Deafness 137 97 9

ZNF423 patient variants, truncations, and in-frame deletions in mice define an allele-dependent range of midline brain abnormalities 137 65 9

Aberrant regulation of a poison exon caused by a non-coding variant in Scn1a-associated epileptic encephalopathy 137 65 49 9

A Drosophila Model of Pontocerebellar Hypoplasia Reveals a Critical Role for the RNA Exosome in Neurons 137 65 49 9 3

Functional Predictors of Causative Cis-Regulatory Mutations in Mendelian Disease 137 65 9

Dominant monoallelic variant in the PAK2 gene causes Knobloch syndrome type 2 137 65 3

Biallelic mutation of CLRN2 causes non-syndromic hearing loss in humans 137 97 9 3

Functional interpretation of ATAD3A variants in neuro-mitochondrial phenotypes 137 97 65 33 9 3

Biallelic variants in the RNA exosome gene EXOSC5 are associated with developmental delays, short stature, cerebellar hypoplasia and motor weakness 137 49 9 3

Homozygote loss-of-function variants in the human COCH gene underlie hearing loss 137 97 3

Patient-specific functional genomics and disease modeling suggest a role for LRP2 in Hypoplastic Left Heart Syndrome 137 57 9 3

CBX1 mutations cause a neurodevelopmental syndrome due to heterochromatin organizational alterations 137 65 9 3

Abnormal expression of GABAA receptor sub-units and hypomotility upon loss of gabra1 in zebrafish. 137 65 3

NCOA3 identified as a new candidate to explain autosomal dominant progressive hearing loss 137 97 9

Functional modeling of NMIHBA-causing PRUNE1 variants reveals a requirement for its exopolyphosphatase activity. 137 65 3

Bi-allelic variants in TSPOAP1, encoding the active zone protein RIMBP1, cause autosomal recessive dystonia 137 65 11 3

Toward the pathogenicity of the SLC26A4 p.C565Y variant using a genetically driven mouse model 137 97 9

Rare variants in dynein heavy chain genes in two individuals with situs inversus and developmental dyslexia 137 97 9

Genes and pathways implicated in tetralogy of Fallot revealed by ultra-rare variant burden analysis in 231 genome sequences 137 97 19 9

Recent ultra-rare inherited mutations identify novel autism candidate risk genes 137 97 19 9

A zebrafish functional genomics model to investigate the role of human A20 variants in vivo 137 97 9 3

A role for the MEGF6 gene in predisposition to osteoporosis 137 97 9

Postembryonic screen for mutations affecting spine development in zebrafish 137 118 20 9 3

Hnrnpul1 loss of function affects skeletal and limb development 137 20 3

Spectrum of genes for inherited hearing loss in the Israeli Jewish population, including the novel human deafness gene ATOH1 137 97 9 5

Novel intramolecular base-pairing of the U8 snoRNA underlies a Mendelian form of cerebral small vessel disease 137 49 3

Interpreting the pathogenicity of Joubert Syndrome missense variants in Caenorhabditis elegans 137 90 9

Mutations in MYLPF cause a novel segmental amyoplasia that manifests as distal arthrogryposis 137 97

Coding de novo mutations identified by WGS reveal novel orofacial cleft genes 137 97 9

Integrative analysis of genomic variants reveals new associations of candidate haploinsufficient genes with congenital heart disease 137 97 9

Novel missense mutation E585K in retinitis pigmentosa leads to compromised RPGR splicing diversity 137 49 9 3

CRISPR Mutants of Three Y Chromosome Genes Suggest Gradual Evolution of Fertility Functions in Drosophila melanogaster 137 21 5

COPB2 haploinsufficiency causes a coatopathy with osteoporosis and developmental delay 137 69 34 3

Locating the sex determining region of linkage group 12 of guppy (Poecilia reticulata) 137 19 5

Negative selection on human genes causing severe inborn errors depends on disease outcome and both the mode and mechanism of inheritance 137 21

Mutations in TMEM43 cause autosomal dominant auditory neuropathy spectrum disorder via interaction with Connexin-mediated passive conductance channels 137 65 9

New genes involved in Angelman syndrome-like: expanding the genetic spectrum 137 65 9

Humanized Drosophila model of the Meier-Gorlin syndrome reveals conserved and divergent features of the Orc6 protein. 137 63 8 3

Cell-based analysis of CAD variants identifies individuals likely to benefit from uridine therapy 137 33

Humanization of Drosophila Gαo to model GNAO1 paediatric encephalopathies 137 33 9

Functional characterization of germline variants in the TMEM127 tumor suppressor reveals novel insights into its membrane topology and trafficking 137 34 3

Identification of MYOM2 as a candidate gene in hypertrophic cardiomyopathy and Tetralogy of Fallot and its functional evaluation in the Drosophila heart 137 3

Spectrum of pathogenic variants and multiple founder effects in amelogenesis imperfecta associated with MMP20 137 97

SORBS2 is a genetic factor contributing to cardiac malformation of 4q deletion syndrome 137 9 3

Strain-dependent modifier genes determine survival in Zfp423 mice 137 65 3

INTS13 Mutations Causing a Developmental Ciliopathy Disrupt Integrator Complex Assembly 137 3

Variants in RABL2A causing male infertility and ciliopathy 137 97 9

Impact of low-frequency coding variants on human facial shape 137 19 9

A novel rare c. -39C>T mutation in the PROS1 5'UTR causing PS deficiency by creating a new upstream translation initiation codon and inhibiting the production of the natural protein. 137 97 9

A novel hypomorphic allele of Spag17 causes primary ciliary dyskinesia phenotypes in mice 137 20 3

Dopachrome tautomerase variants in patients with oculocutaneous albinism. 137 97

A deletion in GDF7 is associated with a heritable forebrain commissural malformation concurrent with ventriculomegaly and interhemispheric cysts in cats. 137 97 9

A novel co-segregating DCTN1 splice site variant in a family with Bipolar Disorder may hold the key to understanding the etiology 137 49 3

De Novo Mutation in an Enhancer of EBF3 in simplex autism 97 9

Identification of Deleterious Single Nucleotide Polymorphism (SNP)s in the Human TBX5 Gene & Prediction of Their Structural & Functional Consequences: An In Silico approach 137 97

Schizophrenia, autism spectrum disorders and developmental disorders share specific disruptive coding mutations 65 9

A genome-wide scan for candidate lethal variants in Thoroughbred horses. 97 9 5

Brain transcriptome analysis reveals subtle effects on mitochondrial function and iron homeostasis of mutations in the SORL1 gene implicated in early onset familial Alzheimers disease 32 9 3

A novel ribosomal protein S20 variant in a family with unexplained colorectal cancer and polyposis 137 97 9

Familial primary ovarian insufficiency associated with a SYCE1 point mutation: Defective meiosis elucidated in humanized mice 137

Germline ERBB3 mutation in familial non-small cell lung carcinoma: expanding the role of the ErbB family in oncogenesis. 137 3

Detecting oncogenic selection through biased allele retention in The Cancer Genome Atlas 97 7 5 4

Hearing impairment due to Mir183/96/182 mutations suggests both loss and gain of function effects 74 65 3

Enhanced activity of glycolytic enzymes in Drosophila and human cell models of Parkinson's disease based on DJ-1 deficiency 54 10 3

Abundance and localization of human UBE3A protein isoforms 65 33 20 3

Neonatal diabetes mutations disrupt a chromatin pioneering function that activates the human insulin gene 137 31 3

Exon 13-skipped USH2A protein retains functional integrity in mice, suggesting an exon skipping therapeutic approach to treat USH2A-associated disease. 72 65 3

Collagen (I) homotrimer does not cause bone fragility but potentiates the osteogenesis imperfecta (oim) mutant allele 137 10

Evolutionary Conservation and Essential Function of Human and Maize RNA Binding Motif Protein 48 (RBM48) in U12-Type Intron Splicing 49 20 3

Effective variant filtering and expected candidate variant yield in studies of rare human disease 165 97 13 4

A forward genetic approach to mapping a P-element second site mutation identifies DCP2 as a novel tumor suppressor in Drosophila melanogaster 137 9 3

Transcription factor-target relationships complicated by knockout analysis 134 9 3

A human TSC1 mutation screening platform in GABAergic cortical interneurons for Genotype to Phenotype assessments 65 11

Modelling the developmental spliceosomal craniofacial disorder Burn-McKeown syndrome using induced pluripotent stem cells 20 9 3

A deep intronic variant activates a pseudoexon in the MTM1 gene in a family with X-linked myotubular myopathy 137 49

Transcriptome analysis of a protein-truncating mutation in sortilin-related receptor 1 associated with early-onset familial Alzheimer's disease indicates effects on mitochondrial and ribosome function in young-adult zebrafish brains 32 9 3

Dissecting Autism Genetic Risk Using Single-cell RNA-seq Data 9 4

The role of KMT2D and KDM6A in cardiac development: A cross-species analysis in humans, mice, and zebrafish 120 9 3

Non-essential function of KRAB zinc finger gene clusters in retrotransposon suppression 137 3

A mouse model of Bardet-Biedl Syndrome has impaired fear memory, which is rescued by lithium treatment 65 11 3

A genome-wide case-only test for the detection of digenic inheritance in human exomes 145 19 4

Genome-wide molecular effects of the neuropsychiatric 16p11 CNVs in an iPSC-to-iN neuronal model 65 9

Ap2s1 mutation in mice causes familial hypocalciuric hypercalcemia type 3 137 65 3

Assessment of autism zebrafish mutant models using a high-throughput larval phenotyping platform 65 33 4

Human iPSC modeling reveals mutation-specific responses to gene therapy in Best disease 33 9

A Bbs5 mouse model reveals pituitary cilia contributions to developmental abnormalities. 65 20 3

The haplolethality paradox of the wupA gene in Drosophila 21 9 5

New pathogenic variants and insights into pathogenic mechanisms in GRK1-related Oguchi disease. 97 9 4

Burden analysis of missense variants in 1,330 disease-associated genes on 3D provides insights into the mutation effects 97 9

Drosophila models of pathogenic copy-number variant genes show global and non-neuronal defects during development 120 9

SFPQ intron retention, reduced expression and aggregate formation in central nervous system tissue are pathological features of amyotrophic lateral sclerosis 61 9 3

A new domestic cat genome assembly based on long sequence reads empowers feline genomic medicine and identifies a novel gene for dwarfism. 97 25 9 4

Respiratory complex and tissue lineage drive mutational patterns in the tumor mitochondrial genome 142 14 9 3

Recessive deleterious variation has a limited impact on signals of adaptive introgression in human populations 21 5 4

Cul3 regulates cytoskeleton protein homeostasis and cell migration during a critical window of brain development 65 11 3 2

PEA15 loss of function and defective cerebral development in the domestic cat 65 3

A complex of distal appendage-associated kinases linked to human disease regulates ciliary trafficking and stability 34 3

Common genetic variants with fetal effects on birth weight are enriched for proximity to genes implicated in rare developmental disorders 19 7 5

Loss of coordinated expression between ribosomal and mitochondrial genes revealed by comprehensive characterization of a large family with a rare mendelian disorder 49 9

Mobile Element Insertions and Associated Structural Variants in Longitudinal Breast Cancer Samples 97 9