KLHL7

INTRODUCTION AND IMPORTANCE: PERCHING syndrome is a condition that affects many parts of the body and is caused by genes passed down from both parents. People with this syndrome have delays in their development, unusual facial features, trouble eating and breathing, slow overall growth, weak muscles, and stiff joints. CASE PRESENTATION: The child at the age of 6 months suffered from developmental delay, delayed walking, speech delay, and hypotonia and was referred to the Neurologist...

Multiple congenital contractures (MCC) due to fetal akinesia manifest across a broad spectrum of diseases, ranging from mild distal arthrogryposis to lethal fetal akinesia deformation sequence. We hereby present a series of 26 fetuses displaying severe MCC phenotypes from 18 families and describe detailed prenatal ultrasound findings, postmortem clinical evaluations, and genetic investigations. Most common prenatal findings were abnormal facial profile (65%), central nervous system abnormalities (62%), polyhydramnios (50%), increased nuchal translucency (50%), and fetal hydrops (35%)...

Many single nucleotide polymorphisms (SNPs) identified by genome-wide association studies exert their effects on disease risk as expression quantitative trait loci (eQTL) via allele-specific expression (ASE). While databases for probing eQTLs in tissues from normal individuals exist, one may wish to ascertain eQTLs or ASE in specific tissues or disease-states not characterized in these databases. Here, we present a protocol to assess ASE of two possible target genes (GPNMB and KLHL7) of a known genome-wide association study (GWAS) Parkinson's disease (PD) risk locus in postmortem human brain tissue from PD and neurologically normal individuals...

Hepatocellular carcinoma (HCC) is a common aggressive tumor with a poor prognosis, and patients often seem to be refractory to the use of therapeutic drugs. In this study, we found that the KLHL7 expression was upregulated in HCC that was associated with poor patient prognosis. KLHL7 has been found to promote HCC development in both in vitro and in vivo experiments. Mechanistically, RASA2, a RAS GAP, was identified as a substrate of KLHL7. Upregulation of KLHL7 by growth factors promotes K48-linked polyubiquitination of RASA2 for degradation via the proteasomal pathway...

Exome sequencing (ES) has become the method of choice for diagnosing rare diseases, while the availability of short-read genome sequencing (SR-GS) in a medical setting is increasing. In addition, new sequencing technologies, such as long-read genome sequencing (LR-GS) and transcriptome sequencing, are being increasingly used. However, the contribution of these techniques compared to widely used ES is not well established, particularly in regards to the analysis of non-coding regions. In a pilot study of five probands affected by an undiagnosed neurodevelopmental disorder, we performed trio-based short-read GS and long-read GS as well as case-only peripheral blood transcriptome sequencing...

BACKGROUND: Asthenozoospermia is a troublesome disease experienced by men in their reproductive years, but its exact etiology remains unclear. To address this problem, this study aims to identify the hub genes and crucial pathways in asthenozoospermia. METHODS: We screened two Gene Expression Omnibus (GEO) datasets (GSE92578 and GSE22331) to extract the differentially expressed genes (DEGs) between normozoospermic and asthenozoospermic men using the "Limma" package...

AIMS: A couple were referred for prenatal genetic testing at 31 weeks gestation due to the presence of mild polyhydramnios and multiple central nervous system (CNS) abnormalities, including borderline ventriculomegaly, possible delayed sulcation, an enlarged cisterna magna and small area of calcification around the posterior horns. Testing was initiated to identify any underlying genetic cause. MATERIALS AND METHODS: Rapid trio exome sequencing (ES) was performed on DNA extracted from parental blood samples and amniotic fluid...

Crisponi / cold-induced sweating syndrome (CS/CISS) is a rare autosomal recessive disorder characterized by episodic hyperthermia, arthrogryposis, impaired feeding ability, and respiratory distress. The classic CS/CISS is mainly associated with CRLF1 and, rarely, CLCF1. PERCHING syndrome, previously known as CS/CISS type-3 associated with biallelic pathogenic variants in KLHL7, is notable for its few overlapping manifestations. This study presents genotype-phenotype relationships in CS/CISS-like spectrum associated with CRLF1 and KLHL7...

PERCHING syndrome is a rare multisystem developmental disorder caused by autosomal recessive (AR) variants (truncating and missense) in the Kelch-like family member 7 gene (KLHL7). We report the first phenotypic and molecular description of PERCHING syndrome in a patient from Central Africa. The patient presented multiple dysmorphic features in addition to neurological, respiratory, gastroenteric, and dysautonomic disorders. Clinical Whole Genome Sequencing in the proband and his mother identified two novel heterozygous variants in the KLHL7 gene, including a maternally inherited intronic variant (NM_001031710...

BACKGROUND: Rapid advances in transcriptomic profiles have resulted in recognizing IRLs (immune-related long noncoding RNAs), as modulators of the expression of genes related to immune cells that mediate immune inhibition as well as immune stimulatory, indicating LncRNAs play fundamental roles in immune modulation. Hence, we establish an IRL classifier to precisely predict prognosis and immunotherapeutic efficiency in laryngeal squamous cell carcinoma (LSCC). METHODS: LSCC RNA-seq (RNA sequencing) datasets, somatic mutation data, and corresponding clinicopathologic information were acquired from TCGA (the Cancer Genome Atlas) and Gene Expression Omnibus (GEO) databases...

RESEARCH QUESTION: Could extracellular vesicle-derived long non-coding RNA (lncRNA) serve as promising circulating biomarkers for endometriosis? DESIGN: To obtain novel diagnostic markers, 85 patients with endometriosis were enrolled as the endometriosis group and 86 unaffected participants as the control group. RNA sequencing was performed to identify extracellular vesicle-derived lncRNA that were differentially expressed between women with endometriosis (n = 5) and unaffected participants (n = 6)...

PURPOSE: Regular exercise affects the expression of several genes, proteins and microRNAs (miRNAs) in time- and intensity-dependent manner promoting longevity. We previously identified from GeneChip Array analysis several differentially expressed genes and miRNAs in muscle from veteran football players (VPG) compared to active untrained elderly subjects (CG); here we focussed on miRNA-1303 (miR-1303). The aims of the present research were: to analyse the effects of football training on the expression of miR-1303 and to identify its putative target involved in the longevity pathways in skeletal muscle from VPG compared to CG...

AIMS: Congenital mesoblastic nephroma (CMN) is histologically classified into classic, cellular and mixed subtypes. The aims of this study were to characterise the clinical, pathological and molecular features of a series of CMNs, and to determine the utility of pan-Trk and epidermal growth factor receptor (EGFR) immunohistochemistry as surrogate markers for NTRK gene fusions and EGFR internal tandem duplications (ITDs). METHODS AND RESULTS: Twenty-two archival CMN cases (12 classic, five cellular, and five mixed) were tested for the ETV6-NTRK3 fusion and EGFR ITD transcripts by the use of reverse transcriptase polymerase chain reaction (PCR), and next-generation sequencing-based anchored multiplex PCR...

To discover driver fusions beyond canonical exon-to-exon chimeric transcripts, we develop CICERO, a local assembly-based algorithm that integrates RNA-seq read support with extensive annotation for candidate ranking. CICERO outperforms commonly used methods, achieving a 95% detection rate for 184 independently validated driver fusions including internal tandem duplications and other non-canonical events in 170 pediatric cancer transcriptomes. Re-analysis of TCGA glioblastoma RNA-seq unveils previously unreported kinase fusions (KLHL7-BRAF) and a 13% prevalence of EGFR C-terminal truncation...

Studies have shown that long non-coding RNA (lncRNA) may act as the carcinogenic factor or tumor suppressor of laryngeal squamous cell carcinoma (LSCC). This study aims to identify the prognostic value and potential target protein-coding genes (PCGs) of lncRNAs in LSCC. The LSCC datasets were collected from The Cancer Genome Atlas (TCGA). Statistical and bioinformatic methods were used to establish and evaluate the prognostic model, identify the correlation between lncRNAs and clinical characteristics, and screen for PCGs co-expressed with lncRNAs...

The bric-a-brac, tramtrack and broad complex (BTB) superfamily of conserved proteins are involved in ubiquitin-proteasome system that contains the Kelch-like (KLHL) gene family. Kelch-like family member 7 (KLHL7), one of the KLHL gene family, consists of one BTB/POZ domain, one BACK domain and five or six Kelch motifs. Numerous variants in KLHL7 gene domains have been reported with Crisponi syndrome/cold-induced sweating syndrome type 1 (CS/CISS1)-like features and retinitis pigmentosa 42, and have recently been identified as causing Bohring-Opitz syndrome (BOS)-like features...

BACKGROUND: Mutations in the Kelch-like protein 7 (KLHL7) represent a recently described and, to date, poorly characterized etiology of inherited retinal dystrophy. Dominant mutations in KLHL7 are a cause of isolated, non-syndromic retinitis pigmentosa (RP). In contrast, recessive loss-of-function mutations are known to cause Crisponi or Bohring-Opitz like cold induced sweating syndrome-3 (BOS-3). In this study, the phenotype and progression of five unrelated patients with KLHL7 mediated autosomal dominant RP (adRP) are characterized...

Crisponi/cold-induced sweating syndrome (CS/CISS) is an autosomal recessive disease characterized by hyperthermia, camptodactyly, feeding and respiratory difficulties often leading to sudden death in the neonatal period. The affected individuals who survived the first critical years of life, develop cold-induced sweating and scoliosis in early childhood. The disease is caused by variants in the CRLF1 or in the CLCF1 gene. Both proteins form a heterodimeric complex that acts on cells expressing the ciliary neurotrophic factor receptor (CNTFR)...

OBJECTIVE: The ubiquitin-proteasome system pathway has been recognised as a crucial cellular mechanism for the proper function of photoreceptor cells. In particular, ubiquitin ligases (E3s) recognise and ubiquitinate specific proteins for degradation. The KLHL7 protein (a BTB-Kelch protein) has been found to play an important role in this process. There have been several reports that heterozygous mutations in the KLHL7 gene in adults are responsible for a rare cause of late-onset autosomal dominant retinitis pigmentosa with preservation of central vision and homozygous mutations in two young children, with Crisponi syndrome (CS)/cold-induced sweating syndrome type 1, result in a recessive form of early-onset peripheral retinal dystrophy type changes...

Crisponi/cold-induced sweating syndrome (CS/CISS) is a rare autosomal recessive disorder characterized by a complex phenotype (hyperthermia and feeding difficulties in the neonatal period, followed by scoliosis and paradoxical sweating induced by cold since early childhood) and a high neonatal lethality. CS/CISS is a genetically heterogeneous disorder caused by mutations in CRLF1 (CS/CISS1), CLCF1 (CS/CISS2) and KLHL7 (CS/CISS-like). Here, a whole exome sequencing approach in individuals with CS/CISS-like phenotype with unknown molecular defect revealed unpredicted alternative diagnoses...