After attachment of its ligand, called sdf1, the cxcr4 protein turns on. More than five hundred of these men would never see another sunset, yet a holiday atmosphere prevailed. Whim arts, w hypogammaglobulinemia, infections, and yelo m kathexis syndrome is a rare combined primary immunodeficiency disease caused by gainoffunction autosomal dominant mutations in cxcr4, a g proteincoupled receptor for the chemokine cxcl12 1. Whim syndrome is a rare primary immunodeficiency disorder. These mutations occur after the last of the seven transmembrane helices, destroying. It is caused by mutations in the chemokine receptor cxcr4, which impair its intracellular trafficking, leading to increased responsiveness to chemokine ligand and retention of. Symptoms usually begin in early childhood with recurrent bacterial infections such as respiratory infections and cellulitis. The treatment of whim syndrome is directed toward the specific symptoms that are. Whim syndrome ws, a rare congenital neutropenia due to mutations of the cxcr4 chemokine receptor, is associated with human papillomavirus hpvinduced warts, hypogammaglobulinemia, bacterial. The immune system is divided into several components, the combined actions of which are responsible for defending against infectious agents. Friday poster two first cases of whim syndrome in ukraine alla volokha shupyk national medical academy of postgraduate education friday poster malignancy in common variable immune deficiency. The term congenital neutropenia encompasses a family of neutropenic disorders, both permanent and intermittent, severe files need to be unzipped before use. Whim syndrome results from autosomal dominant mutations in the gene for the chemokine receptor, cxcr4, resulting in a carboxyterminus truncation of the receptor of between ten and 19 residues. If you like my content and want to support me, consider joining my patreon.
Pdf family trees of the four whim syndrome pedigrees described in this study, consistent with autosomaldominant inheritance and sporadic cases. The cxcr4 mutations in whim syndrome impair the stability. W arts, h ypogammaglobulinemia, recurrent i nfections and m yelokathexis. Pdf description and outcome of a cohort of 8 patients. This susceptibility appears to be associated with a high degree of cellular activation caused by the inability of stromal derived factor 1 sdf1, the natural. Chromothriptic cure of whim syndrome sciencedirect. Whim syndrome or wart, hypogammaglobulinemia, infection, and myelokathexis syndrome is a rare congenital immunodeficiency disorder characterized by chronic noncyclic neutropenia diagnosis. The term whim is an acronym for the main manifestations of the disease. In essence, the patient had deleted the bad copy of the gene and was now cured. She might sweep into the room a halfhour late and everyone must drop everything theyre doing and notice her. Whim syndrome is a rare congenital immunodeficiency disorder characterized by chronic.
Whim syndrome is an autosomal dominant disorder of warts, hypogammaglobulinemia, infections, and myelokathexis caused by heterozygous gainoffunction mutations in the gene encoding the cxcr4 chemokine receptor kawai and malech, 2009. Description and outcome of a cohort of 8 patients with. Whim syndrome warts hyopogammaglobulinemia nfections. Mutations in the chemokine receptor gene cxcr4 are. The icd9 code sets used to report medical diagnoses and inpatient procedures has been replaced by icd10 code sets on october 1, 2015. Whim syndrome ws, a rare congenital neutropenia due to mutations of the cxcr4 chemokine receptor, is associated with human papillomavirus hpvinduced warts, hypogammaglobulinemia, bacterial infections and myelokathexis. Bone marrow exhibits arrest of neutrophil maturation at the promyelocyte or myelocyte stage of development 1.
The molecular defects that underlie these conditions are. Niaid researchers discovered why a woman with whim syndrome was spontaneously cured of the disease. Icd10pcs inpatient procedure coding which is for use in u. These chromosome pairings, which are from her white blood cells, show a normal chromosome 2 on the left, and a truncated chromosome 2 on the right. The use of prophylactic antibiotics in individuals affected with whim has not been specifically studied. Two years ago, a 58yearold woman contacted the national institute of allergy and infectious diseases niaid, where a team of scientists was studying whim syndrome and. Treatment consists on monthly injections of intravenous immunoglobulin. Table 3 shows the tests that could be helpful in patients with wm. Whim syndromes with different genetic anomalies are accounted for by impaired cxcr4. These heterogeneous mutations may be either truncating or frameshift, with potentially different clinical impact17, but are not helpful for wm diagnosis. The cxcr4 gene provides instructions for making a receptor protein that spans the outer membrane of cells, specifically white blood cells and cells in the brain and spinal cord central nervous system. Summary whim syndrome warts, hypogammaglobulinemia, infections, and myelokathexis, a primary immunodeficiency disorder involving. Chromothriptic deletions result in functional cure of whim syndrome. The family trees of the four pedigrees are shown in the additional file2.
Whim syndrome is a rare immunodeficiency disorder, characterized in part by disproportionate susceptibility of epithelial cells to human papillomavirus hpv induced warts. Whim syndrome is an inherited immunodeficiency caused by overactivity of cxcr4, a receptor controlling production and distribution of leukocytes in bone marrow and blood. Wilms tumor, anirida, genitourinary anomalies, and intellectual disability formerly referred to as mental retardation people with wagr syndrome have a 45 to 60 percent chance of developing wilms tumor, a rare form of kidney cancer. Foxs legal counsels said that the said that bi consciously turns a blind eye and deaf ears to reason and evidence, and give in to the whims and caprice of its master in malacantildeang. This type of cancer is most often diagnosed in children but is. Here, we report a case in which chromothripsis spontaneously cured a patient with whim syndrome, an autosomal dominant combined immunodeficiency. Karyotype of a woman spontaneously cured of whim syndrome. The truncation of the receptor protein results in the inability of downregulation after stimulation. Whim syndrome is an immunodeficiency disease characterized by neutropenia, hypogammaglobulinemia and extensive human papillomavirus hpv infection1. Whim syndrome warts, hypogammaglobulinaemia, infections, myelokathexis syndrome xla xlinked agammaglobulinaemia. Mayo clinic and arizona state university alliance for health care brand standards introduction this brand style guide provides standards and guidelines to represent the relationship and activities in the mayo clinic and arizona state university alliance for health care, which is a formal agreement between the two organizations.
Whim syndrome genetic and rare diseases information. Whim syndrome is a rare primary immunodeficiency disorder, which are. Description and outcome of a cohort of 8 patients with whim syndrome from the french severe chronic neutropenia registry. While this treatment shows promise in treating neutropenia decreased white blood cells, this trial. Whim syndrome is a rare, autosomal dominant, immunodeficiency disorder so named. Immunoglobulin replacement therapy and prophylactic antibiotic treatment may. Whim syndrome whim is a congenital immune deficiency with characteristic clinical features that include. Whim syndrome is extremely rare, with 65 cases reported worldwide to date. The long term follow up of eight patients highlights the clinical heterogeneity of this disease as well as the main therapeutic. Family studies of whim syndrome blood american society of.
Data from the ideal patient registry allyson checkley. You can get early access to all future animations and access exclusive patreononly animations and content. Receptor proteins have specific sites into which certain other proteins, called ligands, fit like keys into locks. Whim syndrome is an acronym for a rare immunodeficiency disorder with each letter representing a predominant feature of the condition. What links here related changes upload file special pages permanent link page information wikidata item cite this page. Mayo clinic and arizona state university alliance for. Whim syndrome is a primary immunodeficiency disorder, one of a group of disorders characterized by irregularities in the cell development andor cell maturation process of the immune system. Next generation sequencing panel for inherited bone marrow. By age 6 months, 90% of patients with scn develop bacterial infections such as skin or deep tissue abscesses, oral ulcers and. Whim syndrome caused by a single amino acid substitution in the.
Whim syndrome wiskott aldrich syndrome woods black norbury syndrome. Briefreport defectofplasmacytoiddendriticcellsinwarts. Information specialists, who are masters level oncology professionals, are available to help cancer survivors navigate the best route from diagnosis through treatment, clinical trials and survivorship. The biology and lifecycle of human papillomaviruses. Patients with whim syndrome can be treated with granulocyte colonystimulating factor gcsf. The three patients who received long term gcsf therapy, interrupted treatment in the. Icd10cm diagnosis coding which is for use in all u. European 0rganisation for rare diseases eurordis in brief eurordis is a nongovernmental patientdriven alliance of patient organisations and individuals active in the field of rare diseases, dedicated to improving the quality of life of all people living with rare. This article is from orphanet journal of rare diseases, volume 7. Patients exhibit increased susceptibility to bacterial and viral infections, especially from common serotype human papilloma virus, resulting in warts on the hands and feet starting in childhood. Whim syndrome nord national organization for rare disorders. Chemotaxis defects also include the previously mentioned deficiency of the adhesion molecules and defects. Whim syndrome ws, a rare congenital neutropenia due to.
The walkaway wife syndrome twothirds of all divorces are initiated by women. Her white blood cells were missing a large portion of chromosome 2, where the mutated whim allele resides. Good chair, division chief of pediatric allergy immunology university of south florida at johns hopkins all childrens hospital consultant in immunology, massachusetts general. Severe congenital neutropenia scn is characterized by severe neutropenia at birth 1. Description and outcome of a cohort of 8 patients with whim.
Whim syndrome is due to heterozygous mutations affecting the cterminus of cxcr4, a chemokine receptor mapped on 2q21 locus and expressed by both hematopoietic and nonhematopoietic cells. Molecular signaling section, laboratory of molecular. We identified a whim patient cured by chromothripsis chromosome shattering that fortuitously deleted the abnormal copy of the cxcr4 gene in a single hematopoietic stem cell, which then took over the bone marrow and. If you have problems viewing pdf files, download the latest version of adobe reader.
Pdf chromothriptic cure of whim syndrome researchgate. A case report of a congenital immune deficiency disease whim. Whim syndrome is a rare, autosomal dominant, immunodeficiency disorder sonamed. Mutations in the chemokine receptor gene cxcr4 are associated with whim syndrome, a combined immunodeficiency disease. Whim syndrome is an autosomal dominant combined primary immunodeficiency disease caused by mutations in the chemokine receptor cxcr4 hernandez et al. Wagr syndrome is a disorder that affects many body systems and is named for its main features. Whim warts, hypogammaglobulinemia, infections, myelokathexis syndrome is a rare disease characterized by diverse symptoms indicative of aberrantly functioning immunity. Plerixafor for the treatment of whim syndrome nejm. Clinical considerations in the current international classification more than 200 specific pids are listed spanning nine major categories.
34 857 987 1248 574 1312 814 693 701 1112 1540 147 1231 1153 1196 1011 1199 218 964 85 856 1078 1400 777 692 676 37 1250 69 1557 916 1373 1359 742 348 222 1474 869 30 1296 509 830 804 806 359