Abstract：
AIMS:Congenital neutropenia (CN) is a rare inherited disease that results in recurrent, life-threatening bacterial infections due to a deficiency of mature neutrophils. They are usually caused by heterozygous ELANE mutations although mutations in other genes like HAX-1, G6PC3 and GFI1 have also been reported. Identifying the causative mutation aids in the establishment of diagnosis and rules out other secondary causes of neutropenia like autoimmune cytopenia and evolving aplasia. We aimed to identify the molecular defects in CN patients who had no mutations in ELANE gene, by next generation sequencing (NGS) targeting a customised panel of genes. METHODS:DNA samples were sequenced with an Illumina NextSeq sequencer using an in-house customised panel of genes at ≥100× depth. Bioinformatics analysis was carried out and the pathogenic variants were identified using a stepwise filtering and analysis strategy. Specific mutations identified were subsequently validated by Sanger sequencing. RESULTS:The pathogenic variants identified in the study includes previously reported variants in SBDS (compound heterozygous c.258+2T>C and c.1A>T), GATA2 (heterozygous c.1186C>T) and novel variants in WAS (hemizygous c.812T>C), JAGN1 (homozygous c.70G>A) and RTEL1 (heterozygous c.2893G>C) genes. CONCLUSION:This study highlights that the absence of ELANE mutations does not rule out the diagnosis of CN and this NGS based approach with a customised panel will help in diagnostic confirmation in such patients. The early onset of the disease, clinical severity and associated high risk of malignant transformation in CN strongly suggests the need for early diagnosis and therapeutic intervention.
journal_name
J Clin Patholjournal_title
Journal of clinical pathologyauthors
Arunachalam AK,Suresh H,Edison ES,Korula A,Aboobacker FN,George B,Shaji RV,Mathews V,Balasubramanian Pdoi
10.1136/jclinpath-2019-206306subject
Has Abstractpub_date
2020-06-01 00:00:00pages
322-327issue
6eissn
0021-9746issn
1472-4146pii
jclinpath-2019-206306journal_volume
73pub_type
杂志文章abstract：:Rapid diagnoses were made on 510 breast lumps by three methods in sequence and the results compared with those obtained by paraffin histology.Naked-eye examination of the excised lumps correctly distinguished between benign and malignant tumours in 95.1% of cases with 23 (4.5%) false negative and two (0.4%) false posi...
journal_title：Journal of clinical pathology
pub_type： 杂志文章
doi：10.1136/jcp.26.4.273
更新日期：1973-04-01 00:00:00
abstract：AIMS:To determine whether the monoclonal antibody (MoAb) 83D4, previously shown to be highly specific for carcinoma cells, can be used as an immunocytological marker to discriminate between benign and malignant cells in serous effusions; and to test for a correlation between expression of the antigen reacting with MoAb...
journal_title：Journal of clinical pathology
pub_type： 杂志文章
doi：10.1136/jcp.48.5.433
更新日期：1995-05-01 00:00:00
abstract：:Sections from 100 cervical biopsy specimens were studied by 12 consultant histopathologists to determine the robustness of the existing pathology terminology and classification. Analysis by kappa statistics showed good agreement in the diagnosis of CIN 3 and squamous carcinoma but an inability to distinguish accuratel...
journal_title：Journal of clinical pathology
pub_type： 杂志文章
doi：10.1136/jcp.42.3.231
更新日期：1989-03-01 00:00:00
abstract：:The API 20 STREP system was used to identify 146 known strains from seven species of the genus Listeria, including both pathogenic and environmental strains. The gallery was easy to use and tests, with the exception of leucine arylamidase (LAP) and starch fermentation (AMD), were simple to interpret. Identification to...
journal_title：Journal of clinical pathology
pub_type： 杂志文章
doi：10.1136/jcp.42.5.548
更新日期：1989-05-01 00:00:00
abstract：:The pathological diagnoses and classification schemes for thyroid carcinoma have changed over the past 20 years and continue to do so. New entities have been described and molecular analyses have suggested better characterisation and grouping of certain tumours. Because some of the lesions have been named differently ...
journal_title：Journal of clinical pathology
pub_type： 杂志文章,评审
doi：10.1136/jclinpath-2013-201626
更新日期：2013-09-01 00:00:00
abstract：AIMS:The cell block technique for assessing endoscopic ultrasound-guided fine needle aspiration (EUS-FNA) specimens from pancreatic mucinous cystic lesions (MCLs) was systematically evaluated for the first time, including comparisons with three traditional methods of assessing such specimens. METHODS:The prospective a...
journal_title：Journal of clinical pathology
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doi：10.1136/jclinpath-2019-206079
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journal_title：Journal of clinical pathology
pub_type： 杂志文章
doi：10.1136/jcp.50.8.703
更新日期：1997-08-01 00:00:00
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journal_title：Journal of clinical pathology
pub_type： 杂志文章
doi：10.1136/jcp.49.1.68
更新日期：1996-01-01 00:00:00
abstract：:Although the morphology of the pathognomonic Reed-Sternberg cells of Hodgkin lymphoma (HL) was described over a century ago, it was not until recently that their origin from B lymphocytes was recognised. The demonstration that a proportion of cases of HL harbour the Epstein-Barr virus (EBV) and that its genome is mono...
journal_title：Journal of clinical pathology
pub_type： 杂志文章,评审
doi：10.1136/jcp.2007.050146
更新日期：2007-12-01 00:00:00
abstract：:Eight strains of Pseudomonas putrefaciens have been received from among 466 strains of Pseudomonas submitted to the Computer Trials Laboratory for identification over the last eight years. Two of the strains of P. putrefaciens from patients with otitis media and otitis externa respectively appear to have played a path...
journal_title：Journal of clinical pathology
pub_type： 杂志文章
doi：10.1136/jcp.28.2.149
更新日期：1975-02-01 00:00:00
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journal_title：Journal of clinical pathology
pub_type： 杂志文章,评审
doi：10.1136/jclinpath-2015-203482
更新日期：2016-06-01 00:00:00
abstract：:Platelet transfusions have the highest incidence of post-transfusion sepsis compared with any other blood products. Recent reports suggest that platelet-related bacteraemia occurs at a frequency of approximately 50 times greater than that for red blood cells. The source is usually skin contaminants from the donor and ...
journal_title：Journal of clinical pathology
pub_type： 杂志文章
doi：10.1136/jcp.2007.050492
更新日期：2010-03-01 00:00:00
abstract：:One hundred prostates from 20 to 40 year old men obtained at necropsy were completely sectioned and studied microscopically. Atypical hyperplasia was found in 10 (20%) of 20-29 year old men and in 12 (24%) of 30-40 year old men. The prostates with atypical hyperplasia had similar weights as those without, and the atyp...
journal_title：Journal of clinical pathology
pub_type： 杂志文章
doi：10.1136/jcp.42.4.383
更新日期：1989-04-01 00:00:00
abstract：:A case of signet-ring cell lymphoma affecting bone marrow is reported. The tumour presented as multiple lytic lesions in the lumbosacral spine. A bone biopsy specimen showed the typical appearances of signet-ring cell lymphoma, and the cells stained positively with antiserum to CD20, though neither immunoglobulin ligh...
journal_title：Journal of clinical pathology
pub_type： 杂志文章
doi：10.1136/jcp.47.2.184
更新日期：1994-02-01 00:00:00
abstract：:Sixty six women with first or second trimester fetal loss were investigated for the presence of lupus anticoagulant by routine coagulation tests and the dilute Russell's viper venom time with a platelet neutralisation procedure, and for raised anticardiolipin antibodies by an enzyme linked immunosorbent assay. Of 35 w...
journal_title：Journal of clinical pathology
pub_type： 杂志文章
doi：10.1136/jcp.44.1.45
更新日期：1991-01-01 00:00:00
abstract：:As part of a quality assurance programme at the Aga Khan University Medical Centre, Karachi, Pakistan, all hysterectomy specimens were reviewed from January 1986 to December 1989. Adenomyosis was found in 237 of the 419 (56.5%) specimens studied. Of these 237 patients, 232 (97.9%) were parous and 196 (82.8%) were in t...
journal_title：Journal of clinical pathology
pub_type： 杂志文章
doi：10.1136/jcp.43.10.817
更新日期：1990-10-01 00:00:00
abstract：:One hundred cases of transitional cell carcinoma of the bladder were studied to determine whether squamous metaplasia and other histological features within the bladder can be of value in predicting outcome of treatment with radiotherapy. Sixty cases showed the changes of squamous metaplasia, and of this group 46 (78%...
journal_title：Journal of clinical pathology
pub_type： 杂志文章
doi：10.1136/jcp.42.3.250
更新日期：1989-03-01 00:00:00
abstract：:This report describes a case of mucinous carcinoma and Müllerian metaplasia arising within an appendiceal duplication cyst found incidentally during an emergency Caesarian section. Intestinal duplication cysts are rare and although there are occasional reports of malignant transformation, this is the first case where ...
journal_title：Journal of clinical pathology
pub_type： 信件
doi：10.1136/jcp.55.7.551
更新日期：2002-07-01 00:00:00
abstract：:Veno-occlusive disease of the liver with clinical and pathological features similar to those of the condition occurring in the Caribbean is described in a young woman resident in Britain. The diagnosis was made from liver biopsies and hepatic venography and was confirmed at necropsy. Small amounts of pyrroliziding alk...
journal_title：Journal of clinical pathology
pub_type： 杂志文章
doi：10.1136/jcp.29.9.788
更新日期：1976-09-01 00:00:00
abstract：:We present the pathological findings in a case of acquired immunodeficiency syndrome (AIDS) in a patient with no known risk factor. Postmortem examination showed klebsiella lung abscess, generalised cytomegalovirus infection, cerebral toxoplasmosis, and a primary cerebral lymphoma. An additional feature was the presen...
journal_title：Journal of clinical pathology
pub_type： 杂志文章
doi：10.1136/jcp.37.4.471
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abstract：BACKGROUND:Coronary heart disease is associated with increased B-type natriuretic peptides (BNPs), and, although controversial, may cause exaggerated exercise-induced BNP secretion. We investigated BNP in relation to reversible myocardial ischaemia. MATERIALS AND METHODS:Serum N-terminal proBNP (NT-proBNP) was measure...
journal_title：Journal of clinical pathology
pub_type： 杂志文章
doi：10.1136/jcp.2005.034702
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journal_title：Journal of clinical pathology
pub_type： 杂志文章
doi：10.1136/jcp.2003.012658
更新日期：2004-03-01 00:00:00
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journal_title：Journal of clinical pathology
pub_type： 杂志文章
doi：10.1136/jcp.24.5.472
更新日期：1971-07-01 00:00:00
abstract：:A case of cryptococcal meningo-encephalitis is described. Treatment with the fungicidal agent amphotericin B resulted in temporary improvement, but the patient relapsed and died 17 months after diagnosis. The pathology and treatment of the disease are discussed. ...
journal_title：Journal of clinical pathology
pub_type： 杂志文章
doi：10.1136/jcp.18.3.296
更新日期：1965-05-01 00:00:00
abstract：:Six fetal and 10 neonatal rat or mouse stomachs and a 14-week human fetal stomach were examined for immunofluorescence reactivity with four sera containing parietal cell antibody (PCA) and four other sera containing smooth muscle antibody (SMA). In rat and mouse stomachs, parietal cells first reacted with PCA in 19-da...
journal_title：Journal of clinical pathology
pub_type： 杂志文章
doi：10.1136/jcp.31.6.578
更新日期：1978-06-01 00:00:00
abstract：:A simple, standardised procedure was used for processing data from External Quality Assessment Schemes and for producing performance charts. A graphic presentation of cumulative performance is generated for each test, using an integrated software package to display results in a standardised format. This permits interp...
journal_title：Journal of clinical pathology
pub_type： 杂志文章
doi：10.1136/jcp.44.1.17
更新日期：1991-01-01 00:00:00
abstract：AIMS:To document the features of the so-called aplastic presentation of childhood acute lymphoblastic leukaemia (ALL) and to determine whether this prodrome can be distinguished from aplasia. METHODS:The peripheral blood and bone marrow appearances of all cases of childhood ALL presenting in one health region of Engla...
journal_title：Journal of clinical pathology
pub_type： 杂志文章
doi：10.1136/jcp.45.8.697
更新日期：1992-08-01 00:00:00
abstract：BACKGROUND:An increased level of serum C-reactive protein (CRP) is a known prognostic factor for acute coronary events and sudden cardiac death, and it is associated with coronary calcification. CRP is expressed in coronary arteries, but its role in the development of coronary plaques is unclear. AIM:To investigate CR...
journal_title：Journal of clinical pathology
pub_type： 杂志文章
doi：10.1136/jcp.2006.038729
更新日期：2007-05-01 00:00:00
abstract：AIMS/BACKGROUND:Telomerase, an enzyme associated with cellular immortality, is expressed by most malignant tumours, but is inactive in normal somatic cells except for male germ cells and proliferating stem cells. Thus, the measurement of telomerase activity in tissue samples may provide useful diagnostic and prognostic...
journal_title：Journal of clinical pathology
pub_type： 杂志文章
doi：10.1136/jcp.50.2.110
更新日期：1997-02-01 00:00:00
abstract：AIMS:To determine whether Ki-67 immunoexpression in penile squamous cell carcinoma (PSCC) has a prognostic value and correlates with lymph node metastasis, human papillomavirus (HPV) infection and patient survival. METHODS:148 formalin-fixed paraffin-embedded PSCC samples were tissue-microarrayed, including 97 usual-t...
journal_title：Journal of clinical pathology
pub_type： 杂志文章
doi：10.1136/jclinpath-2011-200638
更新日期：2012-06-01 00:00:00
