Molecular Diagnosis of One Pedigree with Protein S Deficiency and Antithrombin Deficiency

Blood ◽  
2012 ◽  
Vol 120 (21) ◽  
pp. 5140-5140
Author(s):  
Rong-Fu Zhou ◽  
Hong Tao ◽  
Jian Ouyang ◽  
Xian Zhang ◽  
Yonggong Yang ◽  
...  
Keyword(s):  
Conflicts Of Interest ◽  
Novel Mutation ◽  
Color Doppler ◽  
Femoral Vein ◽  
Family Members ◽  
Protein S ◽  
Heterozygous Mutation ◽  
Sequencing Analysis ◽  
Antithrombin Deficiency ◽  
Exon 4

Abstract Abstract 5140 Objective To identify gene mutations for one patient and his family members with protein S and antithrombin deficiency. Methods ELISA were used to detect protein S (PS), protein C (PC) and antithrombin (AT) activities for the proband and family members, respectively. The genomic DNA was extracted from the peripheral blood of proband and family members. All exons and their flanks of protein S gene and antithrombin gene were amplified by polymerase chain reaction (PCR). The PCR products were sequenced directly. The mutation-related exons of his famliy members were amplified by PCR and sequenced directly. Results The proband was a 49-year-old male. He presented with sudden left lower extremity swelling and pain without casues. Regular examination revealed that his APTT, PT, and TT were all in normal levels, but D- dimmer was 5. 62mg/L, Color doppler ultrasonography showed thrombosis in his left femoral vein. The activity of PS for his family members was ‡1 0%, ‡2 0%, ‡3 0%, ‡4 130. 8%, ‡5 8. 4%, ‡1 0%, ‡2 0%, and that of AT was ‡1 129. 1%, ‡2 51. 9%, ‡3 73.2%, ‡4 119. 1%, ‡5 136. 2%, ‡1 65. 5% and ‡2 60. 1%, respectively. The sequencing analysis showed that a heterozygous missense mutation G68395T (NG_009813. 1) was detected in Exon 4 of PS gene leading to the substitution of Arg90 by Leu (NP_000304. 2) for the propositus. The heterozygous mutation (Arg90Leu) was also found in other family members. A heterozygous (nonsense) mutation G12444A (NG_012462. 1) was detected in Exon 4 of AT gene leading to Trp257Ter (NP_000479. 1) for the propositus. The mutation (Trp257Ter) was found in other family members with reduced activity of AT. These two mutations (G68395T in PS gene and G12444A in AT gene) were not reported before and were thus novel ones. Conclusion The novel mutation G68395T in PS gene and G12444A in AT gene might be the causes of deficiency of PS and AT for the family. Disclosures: No relevant conflicts of interest to declare.

scholarly journals The Molecular Diagnosis of Patients with Vein Thrombosis Due to Deficiency of Inherited Anticoagulant Proteins

Blood ◽  
2014 ◽  
Vol 124 (21) ◽  
pp. 1535-1535
Author(s):  
Rong-Fu Zhou ◽  
Bo Gao ◽  
Jian Ou-Yang
Keyword(s):  
Missense Mutation ◽  
Promoter Region ◽  
Protein C ◽  
Conflicts Of Interest ◽  
Genetic Diagnosis ◽  
Protein S ◽  
Deletion Mutation ◽  
Heterozygous Mutation ◽  
Homozygous Mutation ◽  
Thrombin Time

Abstract Objective: To make genetic diagnosis and pedigree analysis for patients with recurrent venous thromboembolism due to inherited deficiency of protein C (PC), protein S (PS). Methods: The routine coagulation tests including activated partial thromboplastin time (APTT), prothrombin time (PT) and thrombin time (TT) were performed. Chromogenic substrate assay was used to detect the activities of Protein C (PC:C), total Protein S (PS:C) and antithrombin (AT:C). All exons and their flanks of PC and PS gene were amplified by polymerase chain reaction (PCR). The PCR products were sequenced directly and blastered to normal sequence of corresponding anti-coagulant protein to find the gene mutations. Results: Totally nine probands with DVT or PE were enrolled, their peripheral blood and medical histories collected after informed consents. Proband 1, 2 and 3 were with combined deficiency of PC and PS, while proband 4 was with PC deficiency. Sequencing of PC gene showed there were polymorphism sites G4880A, C4867T and A5054T in promoter region for all four probands with PC deficiency. PC:C and PS:C for proband 1 was 48% and 26.3%, respectively. PC gene sequencing showed that there was a heterozygous mutation A6578T in exon2 region, resulting in Thr18Ser. Sequencing of PS gene showed there was G68395T heterozygous mutation in exon4 region, leading to Arg90Leu. PC:C and PS:C of proband 2 was 27% and 22.9%, respectively. Heterozygous mutations of G68428A and C68430T in exon4 region of PS gene were found, leading to Arg100His and Gln101Stop, respectively. Proband 3 was with PC deficiency and PS deficiency, PC:C and PS:C were 58% and 57.3%. Heterozygous AGA12702-12704 or AGA12705-12707 deletion mutation was found in Exon2 of PC gene resulting in Arg192del or Arg193del, and heterozygous missense mutation A15240G in Exon9 resulting in His370Arg. Heterozygous mutation G68395T and G825512C was found in Exon4 and Exon9 region of PS gene, respectively, resulting in Arg90Leu and Ser321Thr. Proband 4 was with PC deficiency, PC:C50%. There was no other mutation detected except for polymorphism sites in promoter region. Proband 5 was with PS deficiency, PS:C 38.8%. Heterozygous mutation G68395T in exon4 region was detected, leading to Arg90Leu. Homozygous mutation C102102T was found in Exon14 region,leading to Gla616Val. Proband 6 was with PS deficiency, PS:C 35.2%. Heterozygous mutations G68395T andC68430T in Exon4 were found, leading to Arg90Leu and Gln101Stop, respectively. Proband 7 was with PS deficiency, PS:C 43.7%.Homozygous mutation C102102T in exon14 region was detected, resulting in Gla616Val. Proband 8 was with PS deficiency, PS:C43.6%. Heterozygous mutation G68395T and C68430T in exon4 region was found, leading to Arg90Leu and Gln101Stop. Proband 9 was with PS deficiency, PS:C 7.7%. Two of his family members were also with PS deficiency (II2，III2） with heterozygous mutation G68395T in Exon4 region（II1，II2，III1，III2）, leading to Arg90Leu. Conclusions: Polymorphisms of G4880A, C4867T and A5054T in promoter region, missense mutation A6578T, A15240G, AGA12702-12704 or 12705-12707 deletion mutation in PC gene，missense mutation G68395T, G68428A, C86066T, G82512C, C102102T, and nonsense mutation C68430T in PS gene might be the cause of reduced activities of corresponding anticoagulant proteins. All these mutations, except for C86066T in PS gene, which had been reported in Hongkong, are de novo ones. Disclosures No relevant conflicts of interest to declare.

scholarly journals Severely Impaired Platelet Function Due to a Novel Mutation of P2Y12 from a Human Subject with No History of Bleeding

Blood ◽  
2018 ◽  
Vol 132 (Supplement 1) ◽  
pp. 1130-1130
Author(s):  
John C Kostyak ◽  
Carol A Dangelmaier ◽  
Benjamin R Mauri ◽  
Akruti Patel ◽  
Satya P. Kunapuli
Keyword(s):  
Human Subject ◽  
Conflicts Of Interest ◽  
Novel Mutation ◽  
Platelet Reactivity ◽  
Shape Change ◽  
Human Subjects ◽  
P2y12 Receptor ◽  
Heterozygous Mutation ◽  
Initial Stimulus ◽  
History Of

Abstract Platelets mediate hemostasis through amplifying an initial stimulus and aggregating at a site of injury. The identification of bleeding phenotypes in humans has the potential to reveal new insight into the mechanisms behind platelet signaling, as well as pinpoint new potential therapeutic targets. In fact, the study of bleeding disorders in human subjects has led to the identification of a number of disease states and proteins important to platelet functional responsiveness. We have recently identified a human subject (PDS25) with a platelet functional disorder that has a normal CBC, and no history of bleeding diathesis. However, platelets from PDS25 have virtually no response to even high concentrations of 2-MeSADP, even though P2Y12 protein expression appears unaltered (Figure 1). Further, platelet reactivity to high doses of agonist for other receptors, such as PAR-4 and GPVI, is normal. Low concentrations of these agonists, which typically rely on feedback for platelet reactivity, elicit an inhibited response using platelets from PDS25 compared to platelets from a healthy control. Consistently, Rap1b activity (Figure 2) was reduced in platelets from PDS25, while VASP phosphorylation was enhanced, suggesting that signaling from the P2Y12 receptor was interrupted by the heterozygous mutation. To determine whether it is the receptor or a downstream signaling component that is dysfunctional and because shape change in response to 2-MeSADP is normal in platelets from PDS25, we co-stimulated 2-MeSADP treated platelets with epinephrine to initiate signaling through Gz, which is very similar to Gi. We found that the response of platelets from PDS25 to 2-MeSADP can be rescued with the addition of epinephrine, suggesting that the signaling components downstream of Gi/zare intact. These data suggest that the aberrant reactivity observed in platelets from PDS25 is due to the P2Y12 receptor. Therefore, we performed a genetic analysis of P2Y12 from PDS25, which revealed a heterozygous mutation of D121N within the conserved DRY motif (Figure 3). We are currently evaluating how this heterozygous mutation confers such a strong phenotype. Disclosures No relevant conflicts of interest to declare.

scholarly journals A mutated CRYGD associated with congenital coralliform cataracts in two Chinese pedigrees

2021 ◽  
Vol 14 (6) ◽  
pp. 800-804
Author(s):  
Su-Ping Cai ◽  
◽  
Xi-Zhen Wang ◽  
Yun Wang ◽  
Fen He ◽  
...  
Keyword(s):  
Congenital Cataract ◽  
Autosomal Dominant ◽  
Family Members ◽  
Dominant Mode ◽  
Heterozygous Mutation ◽  
Sequencing Analysis ◽  
Causal Gene ◽  
Exon 2 ◽  
Coding Regions ◽  
Coralliform Cataract

AIM: To investigate the causal gene mutation and clinical characteristics for two Chinese families with autosomal dominant congenital coralliform cataract. METHODS: Two Chinese pedigrees with congenital cataract were investigated. Routine ophthalmic examinations were performed on all patients and non-affected family members. Peripheral blood samples were collected, and the genomic DNAs were extracted. The coding regions of proband’s DNAs were analyzed with cataract gene panel. The identified mutation was amplified by polymerase chain reaction, and automated sequencing was performed in other members of two families to verify whether the mutated gene was co-segregated with the disease. RESULTS: Congenital coralliform cataract was inherited in an autosomal dominant mode in both pedigrees. For each family, more than half of the family members were affected. All patients presented with severe visual impairment after birth as a result of bilateral symmetric coralliform lens opacification. An exact the same defect in the same gene, a heterozygous mutation of c.70C>A (p. P24T) in exon 2 of γD-crystallin gene, was detected in both probands from each family. Sanger sequencing analysis demonstrated that the mutated CRYGD was co-segregated in these two families. CONCLUSION: A c.70C>A (p. P24T) variant in CRYGD gene was reconfirmed to be the causal gene in two Chinese pedigrees. It is known that mutated CRYGD caused most of the congenital coralliform cataracts, suggesting that the CRYGD gene is associated with coralliform congenital cataract.

scholarly journals SAT-351 A Novel Mutation in the Calcium-Sensing Receptor Gene Presenting in a Kindred as Autosomal Dominant Familial Hypocalciuric Hypercalcemia

2020 ◽  
Vol 4 (Supplement_1) ◽  
Author(s):  
Jordan Bushman ◽  
Ajaz Banka
Keyword(s):  
Genetic Analysis ◽  
Novel Mutation ◽  
Receptor Gene ◽  
Family Members ◽  
Heterozygous Mutation ◽  
Familial Hypocalciuric Hypercalcemia ◽  
Loss Of Function ◽  
Calcium Sensing Receptor ◽  
Casr Gene ◽  
Calcium Sensing

Abstract Rationale: Familial hypocalciuric hypercalcemia (FHH) is a benign cause of hypercalcemia. The majority of cases result from an inactivating mutation in the calcium-sensing receptor (CaSR). While affected patients are usually asymptomatic and require no treatment, this condition may go unrecognized and inappropriate parathyroidectomy for presumed primary hyperparathyroidism could be performed. Over 130 mutations in the CaSR gene have been reported and novel variants continue to emerge. Methods: The initial patient was a 49 year-old female who presented with mild hypercalcemia, elevated PTH and undetectable urine calcium. She reported several of her family members had elevated calcium levels. Given high clinical suspicion for FHH genetic analysis was performed. Results: Sequencing of the CaSR gene revealed a point mutation at c.1744T>A which resulted in p.Cys582Ser in exon 7. This cystine residue is highly conserved and predictive algorithms suggest this variant is likely disruptive leading to heterozygous loss of function in the CaSR. The patient’s 26 year-old daughter was tested and found to have the same mutation. Conclusion: We report the identification of a novel heterozygous mutation in the CaSR gene manifesting as FHH in a family of Iraqi decent. Additional family members are currently undergoing genetic analysis which will be included at the time of presentation.

Congenital Hypogonadotropic Hypogonadism with Anosmia and Gorlin Features Caused by a PTCH1 Mutation Reveals a New Candidate Gene for Kallmann Syndrome

2020 ◽  
Vol 111 (1-2) ◽  
pp. 99-114 ◽  
Author(s):  
Sara Barraud ◽  
Brigitte Delemer ◽  
Céline Poirsier-Violle ◽  
Jérôme Bouligand ◽  
Jean-Claude Mérol ◽  
...  
Keyword(s):  
Candidate Gene ◽  
Messenger Rna ◽  
Novel Mutation ◽  
Hypogonadotropic Hypogonadism ◽  
Family Members ◽  
Clinical Signs ◽  
Dominant Mode ◽  
Kallmann Syndrome ◽  
Heterozygous Mutation ◽  
Congenital Hypogonadotropic Hypogonadism

<b><i>Background:</i></b> Two loci (CHD7 and SOX10) underlying Kallmann syndrome (KS) were discovered through clinical and genetic analysis of CHARGE and Waardenburg syndromes, conditions that include congenital anosmia caused by olfactory bulb (CA/OBs) defects and congenital hypogonadotropic hypogonadism (CHH). We hypothesized that other candidate genes for KS could be discovered by analyzing rare syndromes presenting with these signs. <b><i>Study Design, Size, Duration:</i></b> We first investigated a family with Gorlin-Goltz syndrome (GGS) in which affected members exhibited clinical signs suggesting KS. <b><i>Participants/Materials, Methods:</i></b> Proband and family members underwent detailed clinical assessment. The proband received detailed neuroendocrine evaluation. Genetic analyses included sequencing the PTCH1 gene at diagnosis, followed by exome analyses of causative or candidate KS/CHH genes, in order to exclude contribution to the phenotypes of additional mutations. Exome analyses in additional 124 patients with KS/CHH probands with no additional GGS signs. <b><i>Results:</i></b> The proband exhibited CA, absent OBs on magnetic resonance imaging, and had CHH with unilateral cryptorchidism, consistent with KS. Pulsatile Gonadotropin-releasing hormone (GnRH) therapy normalized serum gonadotropins and increased testosterone levels, supporting GnRH deficiency. Genetic studies revealed 3 affected family members harbor a novel mutation of PTCH1 (c.838G&#x3e; T; p.Glu280*). This unreported nonsense deleterious mutation results in either a putative truncated Ptch1 protein or in an absence of translated Ptch1 protein related to nonsense mediated messenger RNA decay. This heterozygous mutation cosegregates in the pedigree with GGS and CA with OBs aplasia/hypoplasia and with CHH in the proband suggesting a genetic linkage and an autosomal dominant mode of inheritance. No pathogenic rare variants in other KS/CHH genes cosegregated with these phenotypes. In additional 124 KS/CHH patients, 3 additional heterozygous, rare missense variants were found and predicted in silico to be damaging: p.Ser1203Arg, p.Arg1192Ser, and p.Ile108Met. <b><i>Conclusion:</i></b> This family suggests that the 2 main signs of KS can be included in GGS associated with PTCH1 mutations. Our data combined with mice models suggest that PTCH1 could be a novel candidate gene for KS/CHH and reinforce the role of the Hedgehog signaling pathway in pathophysiology of KS and GnRH neuron migration.

scholarly journals A Novel Mutation of the Autoimmune Regulator Gene in an Italian Kindred with Autoimmune Polyendocrinopathy-Candidiasis-Ectodermal Dystrophy, Acting in a Dominant Fashion and Strongly Cosegregating with Hypothyroid Autoimmune Thyroiditis

2001 ◽  
Vol 86 (10) ◽  
pp. 4747-4752 ◽  
Author(s):  
Filomena Cetani ◽  
Giuseppe Barbesino ◽  
Simona Borsari ◽  
Elena Pardi ◽  
Luisella Cianferotti ◽  
...  
Keyword(s):  
Autoimmune Thyroiditis ◽  
Novel Mutation ◽  
Direct Sequencing ◽  
Family Members ◽  
Heterozygous Mutation ◽  
Chronic Mucocutaneous Candidiasis ◽  
Regulator Gene ◽  
Coding Region ◽  
Autoimmune Regulator ◽  
Autoimmune Polyendocrinopathy

Autoimmune polyendocrinopathy-candidiasis-ectodermal dystrophy is a rare autosomal recessive disorder characterized by hypoparathyroidism, adrenal failure, chronic mucocutaneous candidiasis, and ectodermal dystrophies and other organ-specific autoimmune diseases. Autoimmune polyendocrinopathy-candidiasis-ectodermal dystrophy is caused by mutations of the autoimmune regulator gene. We identified an Italian family with autoimmune polyendocrinopathy-candidiasis-ectodermal dystrophy and a pattern of inheritance suggestive of a dominant mechanism. Serological and clinical studies showed a high prevalence of hypothyroid autoimmune thyroiditis in affected members with classical autoimmune polyendocrinopathy-candidiasis-ectodermal dystrophy. Direct sequencing of the entire coding region of the autoimmune regulator gene revealed the presence in the proband of a novel missense (G228W) mutation in exon 6 in a heterozygous state. The same heterozygous mutation was identified in all family members with autoimmune polyendocrinopathy-candidiasis-ectodermal dystrophy and/or hypothyroid autoimmune thyroiditis. None of the unaffected family members and 50 unrelated Italian controls carried the mutation. In contrast with all other autoimmune regulator mutations reported in families, the novel G228W mutation acts in a dominant fashion in our family, as only one heterozygous mutation was found in the entire coding sequence of the autoimmune regulator gene in the proband. Moreover, analysis of the family tree showed direct transmission of the hypothyroid autoimmune thyroiditis/polyendocrinopathy-candidiasis-ectodermal dystrophy phenotype to the offspring in each generation in the absence of consanguinity, further supporting a dominant inheritance. The G228W closely cosegregated with hypothyroid autoimmune thyroiditis in our family, whereas a low penetrance of the full autoimmune polyendocrinopathy-candidiasis-ectodermal dystrophy phenotype was observed. In conclusion, we report a novel mutation of the autoimmune regulator gene in a family with autoimmune polyendocrinopathy-candidiasis-ectodermal dystrophy, closely cosegregating with hypothyroid autoimmune thyroiditis. The G228W mutation acts in a dominant fashion and may shed light on the structure-function relationship of the autoimmune regulator protein.

scholarly journals Identification of a Novel Missense KRT12 Mutation in a Vietnamese Family with Meesmann Corneal Dystrophy

2020 ◽  
Vol 11 (1) ◽  
pp. 120-126
Author(s):  
Pham Ngoc Dong ◽  
Le Xuan Cung ◽  
Tran Khanh Sam ◽  
Do Thi Thuy Hang ◽  
Doug D. Chung ◽  
...  
Keyword(s):  
Sanger Sequencing ◽  
Novel Mutation ◽  
Family Members ◽  
Corneal Dystrophy ◽  
Slit Lamp ◽  
Slit Lamp Examination ◽  
Corneal Epithelial ◽  
Epithelial Phenotype ◽  
History Of ◽  
Characteristic Features

Meesmann epithelial corneal dystrophy (MECD) is a rare dominantly inherited disorder that is characterized by corneal epithelial microcysts and is associated with mutations in the keratin 3 (KRT3) and keratin 12 (KRT12) genes. In this study, we report a novel mutation in the KRT12 gene in a Vietnamese pedigree with MECD. Slit-lamp examination was performed on each of the 7 recruited members of a Vietnamese family to identify characteristic features of MECD. After informed consent was obtained from each individual, genomic DNA was isolated from saliva samples and screening of KRT3and KRT12 genes was performed by Sanger sequencing. The proband, a 31-year-old man, complained of a 1-year history of eye irritation and photophobia. Slit-lamp examination revealed intraepithelial microcysts involving only the corneal periphery in each eye with clear central corneas and no stromal or endothelial involvement. Three family members demonstrated similar intraepithelial microcysts, but with diffuse involvement, extended from limbus to limbus. Sanger sequencing of KRT3 (exon 7) and KRT12 (exons 1 and 6) in the proband revealed a novel heterozygous KRT12 variant (c.1273G>A [p.Glu425Lys]) that was present in the three affected family members but was absent in the three family members with clear corneas. This study is the first report of a Vietnamese family affected with MECD, associated with an atypical peripheral corneal epithelial phenotype in the proband and a novel mutation in KRT12.

scholarly journals Novel mutation in the TGFBI gene in a Moroccan family with atypical corneal dystrophy: a case report

2021 ◽  
Vol 14 (1) ◽  
Author(s):  
Yahya Benbouchta ◽  
Imane Cherkaoui Jaouad ◽  
Habiba Tazi ◽  
Hamza Elorch ◽  
Mouna Ouhenach ◽  
...  
Keyword(s):  
Exome Sequencing ◽  
Whole Exome Sequencing ◽  
Clinical Symptoms ◽  
Age Of Onset ◽  
Novel Mutation ◽  
Corneal Dystrophy ◽  
Heterozygous Mutation ◽  
Large Variability ◽  
Whole Exome ◽  
Moroccan Family

Abstract Background Corneal dystrophies (CDs) are a heterogeneous group of bilateral, genetically determined, noninflammatory bilateral corneal diseases that are usually limited to the cornea. CD is characterized by a large variability in the age of onset, evolution and visual impact and the accumulation of insoluble deposits at different depths in the cornea. Clinical symptoms revealed bilateral multiple superficial, epithelial, and stromal anterior granular opacities in different stages of severity among three patients of this family. A total of 99 genes are involved in CDs. The aim of this study was to identify pathogenic variants causing atypical corneal dystrophy in a large Moroccan family and to describe the clinical phenotype with severely different stages of evolution. Case presentation In this study, we report a large Moroccan family with CD. Whole-exome sequencing (WES) was performed in the three affected members who shared a phenotype of corneal dystrophy in different stages of severity. Variant validation and familial segregation were performed by Sanger sequencing in affected sisters and mothers and in two unaffected brothers. Whole-exome sequencing showed a novel heterozygous mutation (c.1772C > A; p.Ser591Tyr) in the TGFBI gene. Clinical examinations demonstrated bilaterally multiple superficial, epithelial and stromal anterior granular opacities in different stages of severity among three patients in this family. Conclusions This report describes a novel mutation in the TGFBI gene found in three family members affected by different phenotypic aspects. This mutation is associated with Thiel-Behnke corneal dystrophy; therefore, it could be considered a novel phenotype genotype correlation, which will help in genetic counselling for this family.

scholarly journals Venous Thromboembolic Disease and Bone Marrow Transplant: A Remarkable Cause of Mortality and Morbidity — Potentially Preventable

Blood ◽  
2018 ◽  
Vol 132 (Supplement 1) ◽  
pp. 5070-5070
Author(s):  
Marta Rivas Luque ◽  
Estefanía Morente Constantin ◽  
Pablo Romero Garcia ◽  
Maria Almudena Garcia-Ruiz ◽  
Manuel Jurado
Keyword(s):  
Medical History ◽  
Conflicts Of Interest ◽  
Protein S ◽  
Marrow Transplant ◽  
Morbidity And Mortality ◽  
Hematopoietic Stem ◽  
Mortality And Morbidity ◽  
Vein Thrombosis ◽  
Venous Thromboembolic ◽  
Hemorrhagic Risk

Abstract Thrombotic events are frequent in patients undergoing HSCT, being an important cause of morbidity and mortality. The highest incidence occurs three months after the transplant. There are several risk factors, which add to those already known for VTE: neoplasia, central venous catheters, immobilization, chemotherapy, infections, GVHD. In the series described, the frequencies are variable, between 0.5 and 23.5%, with an overall incidence of 5%. In patients with GVHD, this incidence increases, with up to 35% of events. METHODS A retrospective observational study that includes patients transplanted in our Unit between 2014 and 2017 has been conducted, with the objective of analyzing the incidence of VTE peri-TPH. Likewise, we have analyzed if it is associated to catheter, presence of CVRF, if there was a known medical history of thrombophilia, number of platelets at time of thrombosis, the heparin used and whether anticoagulation was maintained indefinitely or not. RESULTS Out of the 235 patients included in our series, 130 underwent an autologous transplant and 105 an allogeneic transplant. 18 thrombotic events occurred (9 men and 9 women, aged between 18 and 65 years), which means 7.5% (14 occurred between days 0-100, 12 in patients undergoing autologous hematopoietic stem cell transplantation). Three of them had thromboembolism and the rest deep vein thrombosis, 4 of which with catheter. The platelet count at the time of the event ranges from 21 to 409,000 / mm3. Regarding the heparin used, 2 were treated with Tinzaparin and the rest with Bemiparin. Only 1 of the patients presented prior VTE. Among the patients, there were some with CVRF and others without relevant medical history. Just in one patient, a family thrombophilia study had been performed prior to his hematological diagnosis, resulting in a deficit of protein S. In 8 of the patients, anticoagulation was maintained indefinitely with LMWH in the post-transplant period. CONCLUSIONS Our incidence approaches the literature, albeit the series of published cases are heterogeneous and with variable differences. Although the incidence of thrombosis in these patients is a cause of marked morbidity and mortality, the risk of bleeding also increases, therefore routine prophylaxis is not recommended in all patients. We must undergo an exhaustive analysis of the data to identify individually which patients may be candidates for prophylaxis, with the aim of reducing the incidence without raising the hemorrhagic risk of our patients. Disclosures No relevant conflicts of interest to declare.

scholarly journals Unveiling the 46,XY disorder of sex development patients family with a novel mutation in the GATA4 gene

2021 ◽  
Author(s):  
Liwei Li ◽  
Hui Yang ◽  
Junhong Zhang ◽  
Huijing Lv ◽  
Qing Li ◽  
...  
Keyword(s):  
Karyotype Analysis ◽  
Novel Mutation ◽  
Binding Protein ◽  
Gonadal Development ◽  
Heterozygous Mutation ◽  
Disorder Of Sex Development ◽  
First Report ◽  
Sex Development ◽  
Physical Examinations

Abstract Background GATA-binding protein 4 (GATA4) is the critical regulator in gonadal development and its mutation has been reported related with 46,XY disorder of sex development (DSD). Here, we found the two Chinese cases with 46,XY DSD carried the GATA4 mutation. Physical examinations, B-ultrasound and Karyotype analysis were performed and confirmed the two patients with 46,XY DSD. Results Sequencing were performed and the heterozygous mutation p.Gly375Arg in GATA4 gene was identified in the 2 cases with 46,XY DSD. Their mother was identified carrying the p.Gly375Arg mutation in GATA4 protein. However, their father and litter sister without 46,XY DSD didn’t be found carrying the p.Gly375Arg mutation in GATA4 gene. Conclusion This is the first report that the case with 46,XY DSD carried the mutation Gly375Arg in the GATA4 gene. Our

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