Whim syndrome is a rare primary immunodeficiency disorder, which are disorders in which the bodys immune system does not function properly. Treatment consists on monthly injections of intravenous immunoglobulin, which may reduce. Murphy, chief of niaids laboratory of molecular immunology, were intrigued and began a quest to unravel this medical mystery. Cxcl12 gene encodes a stromal cellderived alpha chemokine, also known as sdf1, a member of the intercrine family. The former mouse models a human disease known as whim warts, hypogammaglobulinemia, infections, myelokathexis syndrome. Plerixafor shows promise as a therapeutic and there is a remarkable report that chromothripsis, a process in which chromosomes undergo extensive rearrangements and deletions, spontaneously cured a whim syndrome patient. The term whim is an acronym for the main manifestations of the disease. Whim syndrome genetic and rare diseases information center. Wpw and preexcitation syndromes kk sethi, a dhall, ds chadha, s garg, sk malani, op mathew abstract wolffparkinsonwhite syndrome is a disorder characterized by presence of an accessory pathway which predisposes patients to tachyarrhythmias and sudden death.
The importance of this pathway has been highlighted by the study of patients with whim syndrome that exhibit a defect in cxcr4 internalization. Whim syndrome is the acronym for warts, hypogammaglobulinemia, infections, myelokathexis. Karyotype of a woman spontaneously cured of whim syndrome. Neutrophils have always been considered as uncomplicated frontline troopers of the innate immune system equipped with limited proinflammatory duties. Term coined by criminologist nils bejerot named after a hostage situation in a bank in stockholm, sweden in august 1973 started to. Symptoms usually begin in early childhood with recurrent bacterial infections such as respiratory infections and cellulitis. The clonal architecture of cxcr4 whim mutations remains to be delineated. The whim syndrome, which features high susceptibility to human papillomavirus hpv infection, is a rare immunodeficiency associated with autosomal dominant heterozygous mutations of the cxcr4 chemokine receptor.
Download pdf 4 mb abstract the chemokine receptor cxcr4 is a widely expressed g proteincoupled receptor that has been implicated in a number of diseases including hiv, cancer, and whim syndrome, with the latter two involving dysregulation of cxcr4 signaling. 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. Adult t cell leukemialymphoma atll is an aggressive malignancy caused by human t cell lymphotropic virus typei htlvi without curative treatment at present. However, there has been little longterm followup of this treatment. There is evidence for the persistance of partial immunodeficiency associated with significant infections, including severe human papillomavirus hpv disease. Whim syndrome warts hyopogammaglobulinemia nfections. Whim syndrome is an autosomal dominant combined primary immunodeficiency disease caused by mutations in the chemokine receptor cxcr4 hernandez et al. Whim syndrome wiskott aldrich syndrome woods black norbury syndrome xlinked agammaglobulinemia. This is an immunodeficiency disorder caused by dominant. Besides properties of the tumor tissue and general antibody pharmacology, a relationship exists between an antibody and its antigen that can shape penetration, catabolism, specificity, and efficacy. Our program was inspired by the goal of helping children and families to. Whim syndrome is a rare, autosomal dominant immunodeficiency which is named for the four key manifestations. Vaccines free fulltext new insights on the emerging.
Whim syndrome or wart, hypogammaglobulinemia, infection, and myelokathexis syndrome is a rare congenital immunodeficiency disorder characterized by chronic noncyclic neutropenia diagnosis. For language access assistance, contact the ncats public information officer. Patient image viewer quick guide healtheconnections. The long term follow up of eight patients highlights the clinical heterogeneity of this disease as well as the main therapeutic. Whim noun definition and synonyms macmillan dictionary. We designed and validated sanger sequencing and pyrosequencing assays to detect mutations in cxcr4 in a clinical laboratory improvement amendmentsapproved clinical. Consistent with nemours familycentered approach, the treatment team provides a thorough evaluation and speci. Recent findings most whim patients have heterozygous cterminus deletion mutations of the intracellular carboxy terminus of the chemokine receptor cxcr4. Clinical validation of a cxcr4 mutation screening assay. These often are very rare disorders which have taught us much about the crucial cellular pathways required for protection against infection from a wide variety of microbes.
C homologous to that found in patients with the disorder termed warts, hypogammaglobulinemia, infections, and myelokathexis whim syndrome 15, for. Whim syndrome whim is a congenital immune deficiency with characteristic clinical features that include. Early characteristics and early screening tools challenges of early diagnosis of autism in virginia the number of 3 years olds diagnosed with autism on december 1, 1999 was 19. The patient reported that from childhood through age 38, she had had many serious infections, often requiring hospitalization, but then none in the 20 subsequent years. Youre either with me or youre against me became danys credo, and those against her were an everchanging multitude to be determined solely by her whims. Haemopoietic stemcell transplantation is a lifesaving treatment for severe combined immune deficiency. Affinity and avidity in antibodybased tumor targeting. Whim syndrome is an autosomal dominant disorder of warts, hypogammaglobulinemia. Preparing my child infants you can help your baby feel more secure during the test if you. Description and outcome of a cohort of 8 patients with. Longterm clinical remission of whim syndrome and evidence for somatic mosaicism in.
Whim syndrome is a rare combined primary immunodeficiency disease. 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 restored. Patients have numerous warts, some venereal, with resultant cervical and vulval premalignant dysplasia. Summary whim syndrome is a rare, autosomal dominant immunodeficiency which is named for the four key manifestations. Immunoglobulin replacement therapy and prophylactic antibiotic treatment may. Whim is an acronym for some of the characteristic symptoms of the disorder warts, hypogammaglobulinemia, infections, and myelokathexis. Whim syndrome is an acronym for a rare immunodeficiency disorder with each letter representing a predominant feature of the condition.
The field of primary immunodeficiency diseases pid has grown dramatically over the past 10 years, the number of defined genetic causes almost doubling to a current total of about different defects. Pdf chromothriptic cure of whim syndrome researchgate. A pivotal role for cxcl12 signaling in hpvmediated. The investor relations website contains information about x4 pharmaceuticals, inc. We report on a kindred of 6 affected individuals in 3 generations with autosomal dominant whim syndrome. Description and outcome of a cohort of 8 patients with whim. Chemokine receptors are gpcrs that are critically involved in leukocyte migration, and their mutation can lead to altered signaling and migratory behavior, leading to immune system impairment.
Cxcr5 and ccr7 serve key developmental roles by regulating the homing of lymphoid tissue inducer lti cells. A collection of disease information resources and questions answered by our genetic and rare diseases information specialists for whim syndrome. We did a retrospective analysis of severe hpv disease in. Ultradeep sequencing for cxcr4 and several polymerase chain reactionbased methods for myd88 revealed that the. Warts, hypogammaglobulinemia, infections, and myelokathexis. 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. Treatment of whim syndrome may include immunoglobulin replacement therapy, granulocyte colony stimulating factor gcsf, or granulocyte macrophage. Whim syndrome is an inherited immunodeficiency caused by overactivity of cxcr4, a receptor controlling production and distribution of leukocytes in bone marrow and blood. 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. Whim syndrome ws, a rare congenital neutropenia due to. Hiv1 nef downmodulates cc and cxc chemokine receptors via ubiquitin and ubiquitinindependent mechanism prabha chandrasekaran1, victoria moore1, monica buckley1, joshua spurrier1, john h.
Warts, hypogammaglobulinemia, infections, and myelokathexis whim syndrome is a rare, autosomal dominant, combined immunodeficiency disorder caused by mutations in the cterminus of cxcr4 that prevent receptor downregulation and therefore result in pathologically increased signaling. Icf syndrome wiskottaldrich syndrome whim syndrome. This family is defined by the location of the first two cysteine residues in the sequence, which are separated by one amino acid cxc chemokinehromas, 1997. Clonal architecture of cxcr4 whimlike mutations in. Current clinical management of whim includes treatment with gcsf, ivig, prophylactic antibiotics, and aggressive surveillance for and surgical extirpation of. Microabstractmutations in cxcr4 have been identified in. Whim syndrome genetic and rare diseases information. A fanciful impulse, or whimsical idea 2019 may 19, alex mclevy, the final game of thrones brings a pensive but simple meditation about stories newbies, in the a. Cxcr4 whim somatic mutations are distinctive to waldenstrom macroglobulinaemia wm, and impact disease presentation and treatment outcome. Chromothriptic cure of whim syndrome sciencedirect. Severe cutaneous papillomavirus disease after haemopoietic. Definition and synonyms of whim from the online english dictionary from macmillan education this is the british english definition of whim.
The truncation of the receptor protein results in the inability of downregulation after stimulation. Of the 60 known individuals with whim syndrome, 29 of whom are patients at the nih, there had been no record of a patient recovering. The three patients who received long term gcsf therapy, interrupted treatment. Whim leukocytes have enhanced responses to cxcl12, the cognate ligand of cxcr4. 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. Patient image viewer quick guide july 2016 healtheconnections introduces patient worklist image viewer, a new feature from healtheconnections that will allow hie users to compare up to four images sidebyside. 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. If you have problems viewing pdf files, download the latest version of adobe reader. Whim syndrome is caused by mutations of the cxcr4 gene that are inherited as an autosomal dominant trait. We developed highly sensitive allelespecific polymerase chain reactionaspcr assays for detecting the most common cxcr4 whim mutations cxcr4 s338x ca and cg in wm. Find, read and cite all the research you need on researchgate.
Cxcl12 and its receptors, cxcr4 and cxcr7, are linked to tumorigenesis, and we reported that abnormal expression of cxcl12 in epidermal keratinocytes. Treatment consists on monthly injections of intravenous immunoglobulin. Cxcr4 mutations interfere with treatment response to ibrutinib. Hypogammaglobulinemia is marked and associated with recurrent upper respiratory infections sinusitis, tonsillitis, otitis media, pneumonia. View american english definition of whim change your default dictionary to american english. 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. Whim syndrome is an immunodeficiency disease characterized by neutropenia, hypogammaglobulinemia, and extensive human papillomavirus hpv infection. This new image viewer will generate a list of all radiological studies that a. Many factors contribute to successful tumor targeting by antibodies. Clinic program the association for x and y chromosome. Whim syndrome is extremely rare, with 65 cases reported worldwide to date. Gainoffunction ccr4 mutations in adult t cell leukemia. A guide to chemokines and their receptors hughes 2018. These mutations closely resemble those occurring in warts, hypogammaglobulinemia, immunodeficiency, and myelokathexis whim syndrome, an immunodeficiency associated with cxcr4 aberrant expression and activity and with chemotherapy resistance in clinical trials.
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