Prevalence of inherited prothrombotic abnormalities and central venous catheter-related thrombosis in haematopoietic stem cell transplants recipients

In this prospective study, we assessed the incidence of central venous catheter (CVC)-related thrombosis in haematopoietic stem cell transplant (HSCT) recipients. We determined the contribution of inherited prothrombotic abnormalities in blood coagulation to CVC-related thrombosis in these patients. The study was conducted between May 2002 and September 2004. CVCs were externalized, nontunneled, polyurethane double lumen catheters. Before catheter insertion, laboratory prothrombotic markers included factor V Leiden, the prothrombin gene Gly20210A mutation, plasma antithrombin levels, and protein C and S activity. All patients were systematically examined by ultrasonography just before, or <24 h after, catheter removal, and in case of clinical signs of thrombosis. A total of 171 patients were included during the 28-month study period. Five (2.9%) and three (1.7%) patients had evidence of protein C and protein S deficiency, respectively. Only one patient had an antithrombin deficiency (0.6%). In total, 10 patients (5.8%) were heterozygous for the factor V Leiden mutation, and one patient had heterozygous prothrombin G20210A mutation (0.6%). We observed a CVC-related thrombosis in 13 patients (7.6%). Thrombosis was diagnosed in four out of 20 patients (20%) with a inherited prothrombotic abnormality compared to nine of 151 patients (6%) who did not have a thrombophilic marker (relative risk 3.3 CI 95% 1.1-9.9). Our results suggest that inherited prothrombotic abnormalities contribute substantially to CVC-related thrombosis in HSCT recipients. In view of physicians' reluctance to prescribe prophylactic anticoagulant treatment in these patients, a priori determination of inherited prothrombotic abnormalities may form a basis to guide these treatment decisions.     

PDS is a new susceptibility gene to autoimmune thyroid diseases: association and linkage study

Autoimmune thyroid disease (AITD), including Graves' disease (GD), Hashimoto thyroiditis (HT), and primary idiopathic myxedema, is caused by multiple genetic and environmental factors. Genes involved in immune response and/or thyroid physiology appear to influence susceptibility to disease. The PDS gene (7q31), responsible for Pendred syndrome (congenital sensorineural hearing loss and goiter), encodes a transmembrane protein known as pendrin. Pendrin is an apical porter of iodide in the thyroid. To evaluate the contribution of PDS gene in the genetic susceptibility of AITD, we examined four microsatellite markers in the gene region. Two hundred thirty-three unrelated patients (GD,141; HT, 54; primary idiopathic myxedema, 38), 15 multiplex AITD families (104 individuals/46 patients) and 154 normal controls were genotyped. Analysis of case-control data showed a significant association of D7S496 and D7S2459 with GD (P = 10(-3)) and HT (P = 1.07 10(-24)), respectively. The family-based association test showed significant association and linkage between AITDs and alleles 121 bp of D7S496 and 173 bp of D7S501. Results obtained by transmission disequilibrium test are in good agreement with those obtained by the family-based association test. Indeed, evidence for linkage and association of allele 121 bp of D7S496 with AITD was confirmed (P = 0.0114). Multipoint nonparametric linkage analysis using MERLIN showed intriguing evidence for linkage with marker D7S496 in families with only GD patients [Z = 2.12, LOD = 0.81, P = 0.026]. Single-point and multipoint parametric LOD score linkage analysis was also performed. Again, the highest multipoint parametric LOD score was found for marker D7S496 (LOD = 1.23; P = 0.0086) in families segregating for GD under a dominant model. This work suggests that the PDS gene should be considered a new susceptibility gene to AITDs with varying contributions in each pathology.     

A Novel Nonsense Mutation in HSD17B3 Gene in a Tunisian Patient with Sexual Ambiguity

Introduction17β‐hydroxysteroid dehydrogenase type 3 (HSD17B3) isoenzyme is present almost exclusively in the testes and converts delta 4 androstenedione to testosterone. Mutations in the HSD17B3 gene cause HSD17B3 deficiency and result in 46,XY Disorders of Sex Development (46,XY DSD).AimThis study aimed to present the clinical and biochemical features of a Tunisian patient who presented a sexual ambiguity orienting to HSD17B3 deficiency and to search for a mutation in the HSD17B3 gene by DNA sequencing.MethodsPolymerase chain reaction (PCR) amplification and subsequent sequencing of all the coding exons of HSD17B3 gene were performed on genomic DNA from the patient, her family, and 50 controls.ResultsGenetic mutation analysis of the HSD17B3 gene revealed the presence of a novel homozygous nonsense mutation in the exon 9 (c.618 C > A) leading to the substitution p.C206X. The mutation p.C206X in the coding exons supports the hypothesis of HSD17B3 deficiency in our patient.ConclusionThe patient described in this study represented a new case of a rare form of 46,XY DSD, associated to a novel gene mutation of HSD17B3 gene. The screening of this mutation is useful for confirming the diagnosis of HSD17B3 deficiency and for prenatal diagnosis. Ben Rhouma B, Belguith N, Mnif MF, Kamoun T, Charfi N, Kamoun M, Abdelhedi F, Hachicha M, Kamoun H, Abid M, and Fakhfakh F. A novel nonsense mutation in HSD17B3 gene in a Tunisian patient with sexual ambiguity. J Sex Med 2013;10:2586–2589.     

Implication of Xenobiotic Metabolizing Enzyme gene (CYP2E1, CYP2C19, CYP2D6, mEH and NAT2) Polymorphisms in Breast Carcinoma

Background  

Xenobiotic Metabolizing Enzymes (XMEs) contribute to the detoxification of numerous cancer therapy-induced products. This study investigated the susceptibility and prognostic implications of the CYP2E1, CYP2C19, CYP2D6, mEH and NAT2 gene polymorphisms in breast carcinoma patients.     

Ultrasound investigation of the rotator cuff after computed arthrotomography coupled to bursography

OBJECTIVES: To evaluate the diagnostic performance of ultrasound rotator cuff imaging after injection of contrast medium into the glenohumeral joint and subacromial bursa. PATIENTS AND METHODS: Twenty-eight patients underwent ultrasonography before and after injection into the glenohumeral joint and subacromial bursa of a mixture of iodinated contrast medium and lidocaine solution. Findings were compared with those from computed tomography of the joint and bursa. RESULTS: Sixteen 16 (16/28, 57%) post-contrast ultrasound scans revealed or confirmed rotator cuff lesions. For supraspinatus and infraspinatus lesions, there were three false-negatives and no false-positives. Three false-negatives were recorded for subscapularis lesions. All false-negatives occurred both before and after the contrast medium injections. CONCLUSION: Injecting contrast medium into the glenohumeral joint and subacromial bursa improves the diagnostic yield of rotator cuff ultrasonography. We suggest that ultrasonography be performed after injections of drugs into the shoulder structures, particularly the subacromial bursa.     

Langerhans cell histiocytois of the thyroid: a rare disease not to be ignored

Thyroid involvement by Langerhans cell histiocytosis is rare. We report the case of a ten-year old boy who presented with a 5 cm goitre. He was treated for diabetes insipidus 14 months before. Thyroid isotopic scan showed hypoactivity of right lobe and revealed a cold left nodule. The patient was treated by right lobo-isthmectomy with adjuvant corticotherapy and chemotherapy (vinblastine). He is well with 12 months follow-up. Microscopic analysis demonstrated a diffuse infiltrate of thyroid parenchyma by sheets of CD1a positive Langerhans cells associated with lymphocyte foci. This case is remarkable by the abundance of Langerhans cells and scarcity of eosinophils. The diagnosis of thyroid langerhans cell histiocytosis should not be ignored in both children and adult patients.     

The primary hereditary form of distal renal tubular acidosis: clinical and genetic studies in 60-member kindred

A distal (type 1) renal tubular acidosis (RTA-1) has been studied in 60 of 69 living members of a large family "HK" and two unrelated small families. The "HK" family, including 28 RTA-1 subjects, presents the first large family with only primary RTA-1 reported to date. The genetic situation in this family confirms the autosomal dominant transmission of the hereditary primary RTA-1 suggested previously on the basis of a few small families. Our data show that, in contrast to the secondary hereditary form, RTA-1 in its primary hereditary form is always complete and often tolerated (asymptomatic). It occurs in non-hypercalciuric families with no clinical variants observed in family members without RTA-1. In our series some clinical abnormalities commonly associated with RTA-1, such as nephrocalcinosis and growth retardation, appeared only in three cases among offspring when both parents were affected. The appearance of such abnormalities, taken as consequences of chronic acidosis in RTA-1, could be favored by the genetic background and/or the homozygosity for the RTA-1 gene. Linkage studies between RTA-1 and 10 genetic markers have been carried out. Results show that only ABO, MNS, GM and RH loci are informative for linkage analysis and none of these loci can be suggested as linked to RTA-1 locus.