Refine
Has Fulltext
- yes (37)
Is part of the Bibliography
- yes (37)
Year of publication
Document Type
- Journal article (37)
Language
- English (37)
Keywords
- DNA methylation (9)
- epigenetics (3)
- Medizin (2)
- STR profile (2)
- bisulfite pyrosequencing (2)
- copy number variation (2)
- exome sequencing (2)
- extracellular matrix (2)
- fetal programming (2)
- fibrosis (2)
- genomic imprinting (2)
- gestational diabetes mellitus (2)
- hearing loss (2)
- hepatic stellate cell (2)
- liver (2)
- methylation (2)
- myofibroblast (2)
- sperm DNA methylation (2)
- (classical and atypical) Werner syndrome (1)
- 3D modeling (1)
- 5-methylcytosine (1)
- ADHD (1)
- ART outcome (1)
- Autism (1)
- Autism spectrum disorders (1)
- BRCA1 (1)
- CAGSSS (1)
- CDC14A (1)
- CLRN2 (1)
- Checkpoints (1)
- Copy number variation (1)
- Cortex (1)
- DFNB32 (1)
- DFNB68 (1)
- DNA Methylation (1)
- DNA damage (1)
- DNA double-strand break (1)
- DNA methylation dynamics (1)
- Damage (1)
- Down syndrome (1)
- Environment (1)
- Epigenetics (1)
- FISH (1)
- Familial Beckwith-Wiedemann syndrome (1)
- Fetal brain development (1)
- Frontal cortex (1)
- GTL2 (1)
- Gecko (1)
- Gene-expression (1)
- Genes (1)
- Genome (1)
- Genotype-phenotype association (1)
- Human prefrontal cortex (1)
- IARS2 (1)
- ICSI (1)
- IMSI (1)
- Instability (1)
- Malignant neoplasms (1)
- Methylome (1)
- Neanderthal (1)
- Pakistan (1)
- Parent-of-origin (1)
- Patterns (1)
- Repair (1)
- S1PR2 (1)
- SKY analysis (1)
- SLC2A3 (1)
- SNP array (1)
- SNP-microarray (1)
- Schizophrenia (1)
- Stability (1)
- Suicidal behavior (1)
- Susceptibility (1)
- Terminal 4q deletion syndrome (1)
- Th17 (1)
- Transcription (1)
- Transcription regulation (1)
- Tregs (1)
- Usher syndrome (1)
- Y chromosome degeneration (1)
- ZW sex chromosomes (1)
- adenoma (1)
- adipose (1)
- adipose tissue dysfunction (1)
- adrenal insufficiency (1)
- age-related differentially methylated regions (ageDMRs) (1)
- alu elements (1)
- antidepressants (1)
- anxiety disorders (1)
- autosomal recessive hearing loss (1)
- autosomal recessive non-synstromic hearing loss (1)
- banding analyses (1)
- blood (1)
- cancer treatment (1)
- cataracts (1)
- childhood cancer (1)
- combined retinal dystrophy (1)
- complex chromosome rearrangements (1)
- complex disorders (1)
- consanguinity (1)
- deafness (1)
- deep bisulfite sequencing (1)
- developmental origins hypothesis (1)
- duplication-deficiency (1)
- epigenetic heterogeneity (1)
- epimutation (1)
- fetal brain development (1)
- fetal cord blood (1)
- fetal overnutrition (1)
- fibroblasts (1)
- frameshift (1)
- frontal cortex (1)
- geckos (1)
- gene (1)
- gene expression (1)
- genetic diagnosis (1)
- genetic heterogeneity (1)
- genetics (1)
- genome-wide association study (GWAS) (1)
- genome-wide linkage analysis (1)
- genotyping arrays (1)
- growth hormone deficiency (1)
- haploinsufficiency (1)
- hearing impairment (1)
- hereditary hearing loss (1)
- heterochromatin (1)
- histological subtype (1)
- human evolution (1)
- hypoxia-inducible factor 3A (1)
- illumina (1)
- in vitro model (1)
- induced pluripotent stem cells (1)
- infinium HumanOmni1-Quad (1)
- inflammatory diseases (1)
- insulin treatment (1)
- karyotype evolution (1)
- mammalian male germline (1)
- meiosis (1)
- meiotic chromosomes (1)
- metabolic disease (1)
- methylation array (1)
- mitotic chromosomes (1)
- mixed hearing loss (1)
- mixed mutation mechanisms (1)
- monozygotic twins (1)
- next generation sequencing (1)
- next-generation sequencing (1)
- non-sense mediated mRNA decay (1)
- obesity (1)
- panic disorder (1)
- paternal age effect (1)
- phalloidin stain (1)
- polymerase chain reaction (1)
- premature aging (1)
- promoter methylation (1)
- protocadherin gamma cluster (1)
- reciprocal translocation (1)
- recombination (1)
- recurrence (1)
- regulatory T cells (1)
- rhodamine–phalloidin stain (1)
- secondary cancer (1)
- segmental progeria (1)
- sensorineural hearing loss (1)
- sensory neuropathy (1)
- sequence alignment (1)
- sex chromosomes (1)
- sex linked pigmentation pattern (1)
- sexual antagonistic genes (1)
- skeletal dysplasia (1)
- somatic mosaicism (1)
- species-specific epigenetic marks (1)
- spectral karyotyping (1)
- sperm (1)
- splicing (1)
- stress fibers (1)
- structural genome variations (1)
- submicroscopic chromosome rearrangement (1)
- suppression (1)
- synaptonemal complex (1)
- systemic sclerosis (1)
- telomere length (1)
- testosterone (1)
- tinnitus (1)
- transcription deficiency (1)
- treatment guidelines (1)
- triplosufficiency (1)
- trisomy 21 (1)
- twin study (1)
- type II esophageal achalasia (1)
- whole exome sequencing (1)
Institute
- Institut für Humangenetik (36)
- Theodor-Boveri-Institut für Biowissenschaften (11)
- Kinderklinik und Poliklinik (2)
- Klinik und Poliklinik für Hals-, Nasen- und Ohrenkrankheiten, plastische und ästhetische Operationen (2)
- Institut für Anatomie und Zellbiologie (1)
- Klinik und Poliklinik für Dermatologie, Venerologie und Allergologie (1)
- Klinik und Poliklinik für Psychiatrie, Psychosomatik und Psychotherapie (1)
- Klinik und Poliklinik für Unfall-, Hand-, Plastische und Wiederherstellungschirurgie (Chirurgische Klinik II) (1)
- Lehrstuhl für Molekulare Psychiatrie (1)
- Medizinische Klinik und Poliklinik II (1)
Sonstige beteiligte Institutionen
Background:
IARS2 encodes a mitochondrial isoleucyl-tRNA synthetase, a highly conserved nuclear-encoded enzyme required for the charging of tRNAs with their cognate amino acid for translation. Recently, pathogenic IARS2 variants have been identified in a number of patients presenting broad clinical phenotypes with autosomal recessive inheritance. These phenotypes range from Leigh and West syndrome to a new syndrome abbreviated CAGSSS that is characterised by cataracts, growth hormone deficiency, sensory neuropathy, sensorineural hearing loss, and skeletal dysplasia, as well as cataract with no additional anomalies.
Methods:
Genomic DNA from Iranian probands from two families with consanguineous parental background and overlapping CAGSSS features were subjected to exome sequencing and bioinformatics analysis.
Results:
Exome sequencing and data analysis revealed a novel homozygous missense variant (c.2625C > T, p.Pro909Ser, NM_018060.3) within a 14.3 Mb run of homozygosity in proband 1 and a novel homozygous missense variant (c.2282A > G, p.His761Arg) residing in an ~ 8 Mb region of homozygosity in a proband of the second family. Patient-derived fibroblasts from proband 1 showed normal respiratory chain enzyme activity, as well as unchanged oxidative phosphorylation protein subunits and IARS2 levels. Homology modelling of the known and novel amino acid residue substitutions in IARS2 provided insight into the possible consequence of these variants on function and structure of the protein.
Conclusions:
This study further expands the phenotypic spectrum of IARS2 pathogenic variants to include two patients (patients 2 and 3) with cataract and skeletal dysplasia and no other features of CAGSSS to the possible presentation of the defects in IARS2. Additionally, this study suggests that adult patients with CAGSSS may manifest central adrenal insufficiency and type II esophageal achalasia and proposes that a variable sensorineural hearing loss onset, proportionate short stature, polyneuropathy, and mild dysmorphic features are possible, as seen in patient 1. Our findings support that even though biallelic IARS2 pathogenic variants can result in a distinctive, clinically recognisable phenotype in humans, it can also show a wide range of clinical presentation from severe pediatric neurological disorders of Leigh and West syndrome to both non-syndromic cataract and cataract accompanied by skeletal dysplasia.