Read by QxMD icon Read


Rena J Vanzo, Hope Twede, Karen S Ho, Aparna Prasad, Megan M Martin, Sarah T South, E Robert Wassman
Copy number variants (CNV)s involving KANK1 are generally classified as variants of unknown significance. Several clinical case reports suggest that the loss of KANK1 on chromosome 9p24.3 has potential impact on neurodevelopment. These case studies are inconsistent in terms of patient phenotype and suspected pattern of inheritance. Further complexities arise because these published reports utilize a variety of genetic testing platforms with varying resolution of the 9p region; this ultimately causes uncertainty about the impacted genomic coordinates and gene transcripts...
May 2, 2018: European Journal of Medical Genetics
Naoto Kubota, Toshifumi Yokoyama, Nobuhiko Hoshi, Mikita Suyama
Cerebral palsy (CP) is a major neuronal disease and the most common movement disorder in children. Although environmental factors leading to CP have been greatly investigated, the genetic mechanism underlying CP is not well understood. Here we focused on two clinical reports that characterized a deletion involving the KANK1 gene locus in the 9p24.3 region. One report shows spastic CP and the other shows no spastic CP phenotype. Based on the epigenetic status and evolutionary conservation, we first found a functional genomic element at the noncoding region that was deleted only in patients with spastic CP...
January 29, 2018: Biochemical and Biophysical Research Communications
Matthew Jensen, Santhosh Girirajan
Distinct neurodevelopmental disorders have a common genetic etiology that explains the high degree of comorbidity among these disorders. A recent study sought to identify copy number variants across five neurodevelopmental disorders, and detected an enrichment for chromosome 9p24.3 duplication encompassing DOCK8 and KANK1 in affected individuals. Such large-scale studies will help uncover additional causative and modifier loci within common pathways, which will enable the development of therapeutic targets for the treatment of multiple disorders...
December 14, 2017: Genome Medicine
Wenfei Pan, Kang Sun, Kun Tang, Qingpin Xiao, Chenxue Ma, Cong Yu, Zhiyi Wei
Kidney ankyrin repeat-containing proteins (KANK1/2/3/4) belong to a family of scaffold proteins, playing critical roles in cytoskeleton organization, cell polarity, and migration. Mutations in KANK proteins are implicated in cancers and genetic diseases, such as nephrotic syndrome. KANK proteins can bind various target proteins through different protein regions, including a highly conserved ankyrin repeat domain (ANKRD). However, the molecular basis for target recognition by the ANKRD remains elusive. In this study, we solved a high-resolution crystal structure of the ANKRD of KANK1 in complex with a short sequence of the motor protein kinesin family member 21A (KIF21A), revealing that the highly specific target-binding mode of the ANKRD involves combinatorial use of two interfaces...
February 9, 2018: Journal of Biological Chemistry
Joseph T Glessner, Jin Li, Dai Wang, Michael March, Leandro Lima, Akshatha Desai, Dexter Hadley, Charlly Kao, Raquel E Gur, Nadine Cohen, Patrick M A Sleiman, Qingqin Li, Hakon Hakonarson
BACKGROUND: Neurodevelopmental and neuropsychiatric disorders represent a wide spectrum of heterogeneous yet inter-related disease conditions. The overlapping clinical presentations of these diseases suggest a shared genetic etiology. We aim to identify shared structural variants spanning the spectrum of five neuropsychiatric disorders. METHODS: We investigated copy number variations (CNVs) in five cohorts, including schizophrenia (SCZ), bipolar disease (BD), autism spectrum disorders (ASD), attention deficit hyperactivity disorder (ADHD), and depression, from 7849 cases and 10,799 controls...
November 30, 2017: Genome Medicine
Qiong Guo, Shanhui Liao, Zhongliang Zhu, Yue Li, Fudong Li, Chao Xu
A well-controlled microtubule organization is essential for intracellular transport, cytoskeleton maintenance, and cell development. KN motif and ankyrin repeat domain-containing protein 1 (KANK1), a member of KANK family, recruits kinesin family member 21A (KIF21A) to the cell cortex to control microtubule growth via its C-terminal ankyrin domain. However, how the KANK1 ankyrin domain recognizes KIF21A and whether other KANK proteins can also bind KIF21A remain unknown. Here, using a combination of structural, site-directed mutagenesis, and biochemical studies, we found that a stretch of ∼22 amino acids in KIF21A is sufficient for binding to KANK1 and its close homolog KANK2...
January 12, 2018: Journal of Biological Chemistry
Zhuangfeng Weng, Yuan Shang, Deqiang Yao, Jinwei Zhu, Rongguang Zhang
The cross-talk between dynamic microtubules and the cell cortex plays important roles in cell division, polarity, and migration. A critical adaptor that links the plus ends of microtubules with the cell cortex is the KANK N-terminal motif and ankyrin repeat domains 1 (KANK1)/kinesin family member 21A (KIF21A) complex. Genetic defects in these two proteins are associated with various cancers and developmental diseases, such as congenital fibrosis of the extraocular muscles type 1. However, the molecular mechanism governing the KANK1/KIF21A interaction and the role of the conserved ankyrin (ANK) repeats in this interaction are still unclear...
January 5, 2018: Journal of Biological Chemistry
Kevin Lai, Catherine A Harwood, Karin J Purdie, Charlotte M Proby, Irene M Leigh, Namita Ravi, Thaddeus W Mully, Lionel Brooks, Priscilla M Sandoval, Michael D Rosenblum, Sarah T Arron
Atypical fibroxanthoma (AFX), is a rare type of skin cancer affecting older individuals with sun damaged skin. Since there is limited genomic information about AFX, our study seeks to improve the understanding of AFX through whole-exome and RNA sequencing of 8 matched tumor-normal samples. AFX is a highly mutated malignancy with recurrent mutations in a number of genes, including COL11A1, ERBB4, CSMD3, and FAT1. The majority of mutations identified were UV signature (C>T in dipyrimidines). We observed deletion of chromosomal segments on chr9p and chr13q, including tumor suppressor genes such as KANK1 and CDKN2A, but no gene fusions were found...
2017: PloS One
Tao Chen, Kun Wang, Xianzhou Tong
Recent research has found that Kank1 gene, as one of the important members of the Kank gene family, plays an important role in the occurrence and development of malignant tumors. As a brand new cancer suppressor gene, its expression is significantly downregulated or missing in various kinds of malignant tumors. However, no report on the specific role of Kank1 in the genesis and development of gastric cancer is available yet. In the present study, we found significantly lower expression of Kank1 gene in human gastric cancer cells...
July 17, 2017: Oncology Reports
Aida Catic, Amina Kurtovic-Kozaric, Sarah H Johnson, George Vasmatzis, Michael R Pins, Jillene Kogan
Renal metanephric adenoma (MA) is a rare benign tumor frequently misclassified when microscopic features alone are applied. The correct classification of a renal tumor is critical for diagnostic, prognostic, and therapeutic purposes. Despite the advancements in cancer genomics, up until recently relatively few genetic alterations critical to MA development have been recognized. Recent data suggest that 90% of MA have BRAF(V600E) mutations; the genetics of the remaining 10% are unclear. To date, only one case of a chromosomal translocation, t(9;15)(p24;q24) associated with MA has been reported...
August 2017: Cancer Genetics
Zhibin Cui, Yingjia Shen, Kenny H Chen, Suresh K Mittal, Jer-Yen Yang, GuangJun Zhang
No abstract text is available yet for this article.
April 24, 2017: Scientific Reports
Jun-Ichiro Suzuki, Badal Chandra Roy, Takunori Ogaeri, Naoto Kakinuma, Ryoiti Kiyama
Chromosome instability, frequently found in cancer cells, is caused by a deficiency in cell division, including centrosomal amplification and cytokinesis failure, and can result in abnormal chromosome content or aneuploidy. The small GTPase pathways have been implicated as important processes in cell division. We found that knockdown of a tumor suppressor protein Kank1 increases the number of cells with a micronucleus or bi-/multi-nuclei, which was likely caused by centrosomal amplification. Kank1 interacts with Daam1, known to bind to and activate a small GTPase, RhoA, in actin assembly...
April 15, 2017: Experimental Cell Research
Zhibin Cui, Yingjia Shen, Kenny H Chen, Suresh K Mittal, Jer-Yen Yang, GuangJun Zhang
Malignant peripheral nerve sheath tumors (MPNSTs) are a type of rare sarcomas with a poor prognosis due to its highly invasive nature and limited treatment options. Currently there is no targeted-cancer therapy for this type of malignancy. Thus, it is important to identify more cancer driver genes that may serve as targets of cancer therapy. Through comparative oncogenomics, we have found that KANK1 was a candidate tumor suppressor gene (TSG) for human MPNSTs. Although KANK1 is known as a cytoskeleton regulator, its tumorigenic function in MPNSTs remains largely unknown...
January 9, 2017: Scientific Reports
Jia-Chi Wang, Loretta W Mahon, Leslie P Ross, Arturo Anguiano, Renius Owen, Fatih Z Boyar
BACKGROUND: High-resolution oligo-SNP array allowed the identification of extremely small pathogenic deletions at numerous clinically relevant regions. In our clinical practice, we found that small pathogenic deletions were frequently encountered at chromosome 9p and 9q terminal regions. RESULTS: A review of 531 cases with reportable copy number changes on chromosome 9 revealed142 pathogenic copy number variants (CNVs): 104 losses, 31 gains, 7 complex chromosomal rearrangements...
2016: Molecular Cytogenetics
Chih-Ping Chen, Chen-Ju Lin, Schu-Rern Chern, Peih-Shan Wu, Yen-Ni Chen, Shin-Wen Chen, Chen-Chi Lee, Li-Feng Chen, Chien-Wen Yang, Wayseen Wang
OBJECTIVE: We present molecular cytogenetic characterization of a prenatally detected derivative chromosome 9 [der(9)] of unknown origin. CASE REPORT: A 35-year-old woman underwent amniocentesis at 18 weeks of gestation because of advanced maternal age, which revealed a der(9) chromosome of unknown origin. The parental karyotypes were normal. Array comparative genomic hybridization (aCGH) analysis revealed a 2.593 Mb deletion of 9p24.3-p24.2 encompassing DOCK8, KANK1, DMRT1, and VLDLR and a 16...
August 2016: Taiwanese Journal of Obstetrics & Gynecology
Benjamin P Bouchet, Rosemarie E Gough, York-Christoph Ammon, Dieudonnée van de Willige, Harm Post, Guillaume Jacquemet, Af Maarten Altelaar, Albert Jr Heck, Benjamin T Goult, Anna Akhmanova
The cross-talk between dynamic microtubules and integrin-based adhesions to the extracellular matrix plays a crucial role in cell polarity and migration. Microtubules regulate the turnover of adhesion sites, and, in turn, focal adhesions promote the cortical microtubule capture and stabilization in their vicinity, but the underlying mechanism is unknown. Here, we show that cortical microtubule stabilization sites containing CLASPs, KIF21A, LL5β and liprins are recruited to focal adhesions by the adaptor protein KANK1, which directly interacts with the major adhesion component, talin...
July 13, 2016: ELife
Monica R Hensley, Zhibin Cui, Rhys F M Chua, Stefanie Simpson, Nicole L Shammas, Jer-Yen Yang, Yuk Fai Leung, GuangJun Zhang
Gene co-option, usually after gene duplication, in the evolution of development is found to contribute to vertebrate morphological innovations, including the endothelium-based vascular system. Recently, a zebrafish kank gene was found expressed in the vascular vessel primordium, suggesting KANK genes are a component of the developmental tool kit for the vertebrate vascular system. However, how the KANK gene family is involved in vascular vessel development during evolution remains largely unknown. First, we analyzed the molecular evolution of the KANK genes in metazoan, and found that KANK1, KANK2, KANK3 and KANK4 emerged in the lineage of vertebrate, consistent with the two rounds of vertebrate whole-genome duplications (WGD)...
June 13, 2016: Scientific Reports
Kubra Karagoz, Heather L Lehman, Douglas B Stairs, Raghu Sinha, Kazim Y Arga
Esophageal squamous cell carcinoma (ESCC), which is the most common subtype of esophageal cancers, is the sixth leading cause of cancer death worldwide with a five-year survival rate of 19%. Identification of efficient biomarkers for early detection and better understanding of the molecular mechanisms of ESCC may offer reduced mortality. However, proper biomarkers for clinical diagnosis and prognosis have not been defined yet. In the presented study, we employed a systematic and integrative 'omics' strategy to reconstruct networks of transcriptional regulation and protein-protein interaction to identify novel biomarkers, potential molecular targets, and mechanisms of transcriptional control in ESCC...
February 2, 2016: Current Cancer Drug Targets
Elisa Tassano, Andrea Accogli, Marco Pavanello, Claudio Bruno, Valeria Capra, Giorgio Gimelli, Cristina Cuoco
Chromosome 9p deletion represents a clinically and genetically heterogeneous condition characterized by a wide spectrum of phenotypic manifestations and a variable size of the deleted region. The deletion breakpoint occurs from 9p22 to 9p24 bands, and the large majority of cases have either terminal deletions or translocations involving another chromosome. Here we report on two patients with similar inherited interstitial 9p24.3 deletion involving only DOCK8 and KANK1 genes. Interestingly, the two patients showed non-overlapping phenotypic traits ranging from a complex phenotype in one to only trigonocephaly with minor dysmorphic features and hand anomalies in the other one...
January 2016: European Journal of Medical Genetics
Karl Martin Klein, Manuela Pendziwiat, Rony Cohen, Silke Appenzeller, Carolien G F de Kovel, Felix Rosenow, Bobby P C Koeleman, Gregor Kuhlenbäumer, Liron Sheintuch, Ronel Veksler, Alon Friedman, Zaid Afawi, Ingo Helbig
We report a new family with autosomal dominant epilepsy with auditory features (ADEAF) including focal cortical dysplasia (FCD) in the proband. We aim to identify the molecular cause in this family and clarify the relationship between FCD and ADEAF. A large Iranian Jewish family including 14 individuals with epileptic seizures was phenotyped including high-resolution 3-T MRI. We performed linkage analysis and exome sequencing. LGI1, KANK1 and RELN were Sanger sequenced. Seizure semiology of 11 individuals was consistent with ADEAF...
January 2016: Journal of Neurology
Fetch more papers »
Fetching more papers... Fetching...
Read by QxMD. Sign in or create an account to discover new knowledge that matter to you.
Remove bar
Read by QxMD icon Read

Search Tips

Use Boolean operators: AND/OR

diabetic AND foot
diabetes OR diabetic

Exclude a word using the 'minus' sign

Virchow -triad

Use Parentheses

water AND (cup OR glass)

Add an asterisk (*) at end of a word to include word stems

Neuro* will search for Neurology, Neuroscientist, Neurological, and so on

Use quotes to search for an exact phrase

"primary prevention of cancer"
(heart or cardiac or cardio*) AND arrest -"American Heart Association"