scholarly journals Solid Pseudopapillary Neoplasm of the Pancreas and Abdominal Desmoid Tumor in a Patient Carrying Two Different BRCA2 Germline Mutations: New Horizons from Tumor Molecular Profiling

Genes ◽  
2021 ◽  
Vol 12 (4) ◽  
pp. 481
Author(s):  
Andrea Mafficini ◽  
Rita T. Lawlor ◽  
Claudio Ghimenton ◽  
Davide Antonello ◽  
Cinzia Cantù ◽  
...  
Keyword(s):  
Somatic Mutation ◽  
Desmoid Tumor ◽  
Germline Mutations ◽  
Molecular Profiling ◽  
Splice Acceptor Site ◽  
Acceptor Site ◽  
Solid Pseudopapillary Neoplasm ◽  
Her Family ◽  
History Of ◽  
Abdominal Desmoid Tumor

This case report describes the history of a 41 year-old woman with a solid pseudopapillary neoplasm (SPN) of the pancreas and a metachronous abdominal desmoid tumor (DT) that occurred two years after the SPN surgical resection. At next-generation sequencing of 174 cancer-related genes, both neoplasms harbored a CTNNB1 somatic mutation which was different in each tumor. Moreover, two BRCA2 pathogenic mutations were found in both tumors, confirmed as germline by the sequencing of normal tissue. The BRCA2 mutations were c.631G>A, resulting in the amino-acid change p.V211I, and c.7008-2A>T, causing a splice acceptor site loss. However, as the two neoplasms showed neither loss of heterozygosity nor somatic mutation in the second BRCA2 allele, they cannot be considered as BRCA-dependent tumors. Nevertheless, this study highlights the important opportunities opened by extensive tumor molecular profiling. In this particular case, it permitted the detection of BRCA2-germline mutations, essential for addressing the necessary BRCA-related genetic counseling, surveillance, and screening for the patient and her family.

Solid pseudopapillary neoplasm of the pancreas and abdominal desmoid tumor in a patient carrying two different BRCA2 germline mutations

Pancreatology ◽  
2021 ◽  
Vol 21 ◽  
pp. S63
Author(s):  
A. Mafficini ◽  
C. Ghimenton ◽  
D. Antonello ◽  
C. Cantù ◽  
R. Salvia ◽  
...  
Keyword(s):  
Desmoid Tumor ◽  
Germline Mutations ◽  
Solid Pseudopapillary Neoplasm ◽  
Abdominal Desmoid Tumor

scholarly journals Case Report: A Case of Intra-Abdominal Desmoid Tumor in a Young Woman with No History of Open Surgery

2015 ◽  
Vol 40 (5) ◽  
pp. 994-1001 ◽  
Author(s):  
Kazuki Hashimoto ◽  
Takashi Oshima ◽  
Amane Kanazawa ◽  
Teni Godai ◽  
Naoto Yamamoto ◽  
...  
Keyword(s):  
Case Report ◽  
Young Woman ◽  
Desmoid Tumor ◽  
Open Surgery ◽  
History Of ◽  
Abdominal Desmoid Tumor

Identification of Two New DBA Genes, RPS27 and RPL27, by Whole-Exome Sequencing in Diamond-Blackfan Anemia Patients

Blood ◽  
2012 ◽  
Vol 120 (21) ◽  
pp. 984-984 ◽  
Author(s):  
Etsuro Ito ◽  
Kenichi Yoshida ◽  
Yusuke Okuno ◽  
Aiko Sato-Otsubo ◽  
Tsutomu Toki ◽  
...  
Keyword(s):  
Exome Sequencing ◽  
Whole Exome Sequencing ◽  
Germline Mutations ◽  
Steroid Treatment ◽  
Single Amino Acid ◽  
Splice Acceptor Site ◽  
Acceptor Site ◽  
Diamond Blackfan Anemia ◽  
Whole Exome ◽  
Increased Risk

Abstract Abstract 984 Diamond-Blackfan anemia (DBA) is a congenital bone marrow failure syndrome, characterized by red blood cell aplasia, macrocytic anemia, and increased risk of malignancy. Approximately 90% of patients present during the first year of life or in early childhood. About 40–50% of DBA cases are familial with autosomal dominant, while the remainder is sporadic cases whose mode of inheritance is largely unknown. Although anemia is the most prominent feature of DBA, up to 40% of patients also accompany other symptoms including growth retardation and/or a variety of congenital malformations. Recent studies have shown that the disease could be associated with heterozygous mutations in ribosomal protein (RP) genes, including six small subunit RP genes RPS7, RPS10, RPS17, RPS19, RPS24, and RPS26 as well as four large subunit RP genes RPL5, RPL11, RPL26, and RPL35A, which collectively account for about 50% of patients with DBA. In addition, germline mutations in the GATA1 gene encoding a hematopoietic transcription factor, have been also reported in two DBA families. However, it is clear that the molecular etiology of many DBA cases remains to be covered. To identify new mutations that are responsible for DBA, we performed whole-exome sequencing on 40 DBA patients with no documented mutations/deletions involving known DBA genes. After excluding all variants registered in the 1000 Genomes Project, or dbSNP131, or found in our inhouse SNP database, we searched for non-synonymous mutations involving RP genes as possible candidate for novel DBA genes. In this study, we identified probable pathogenic mutations in two novel RP genes, RPS27 and RPL27 in two patients. The first case was a 1-year-old girl who harbored a single nucleotide substitution at the splice acceptor site in intron 1 of RPL27 (c.-2–1G>A), which results in splicing error. She had atrial septal defect and pulmonary stenosis, and responded to steroid treatment. The second case was a 2-year-old girl carrying a frameshift deletion of RPS27 (c.90delC, p.Tyr31ThrfsX5), leading to a premature truncation. This patient had no abnormalities and responded to steroid treatment. An additional five missense SNVs affecting single cases was identified in five genes, including RPL3L, RPL8, RPL13, RPL18A, and RPL31, together with two in-frame deletions of RPL6 and RPL14 in two patients, which cause deletion of a single amino-acid. However, the pathological significance in these 7 cases is uncertain. In the remaining 31 patients, no mutations were detected in RP genes. In conclusion, we identified novel germline mutations of RP genes that could be responsible for DBA, further confirming the concept that the RP genes are common targets of germline mutations in DBA patients and also suggested the presence of non-RP gene targets for DNA. Disclosures: No relevant conflicts of interest to declare.

scholarly journals Germline inactivating mutations of the aryl hydrocarbon receptor-interacting protein gene in a large cohort of sporadic acromegaly: mutations are found in a subset of young patients with macroadenomas

2007 ◽  
Vol 157 (1) ◽  
pp. 1-8 ◽  
Author(s):  
Laure Cazabat ◽  
Rossella Libè ◽  
Karine Perlemoine ◽  
Fernande René-Corail ◽  
Nelly Burnichon ◽  
...  
Keyword(s):  
Aryl Hydrocarbon Receptor ◽  
Protein Gene ◽  
Mutation Screening ◽  
Germline Mutations ◽  
Large Cohort ◽  
Splice Acceptor Site ◽  
Acceptor Site ◽  
Interacting Protein ◽  
Aryl Hydrocarbon ◽  
Exon 4

Objective: Germline mutations of the aryl hydrocarbon receptor-interacting protein gene (AIP) have recently been described in three families with GH or prolactin-secreting tumors, as well as in a few patients with apparently sporadic somatotropinomas. The aim of the study was to determine the prevalence of AIP mutations in a large cohort of patients with apparently sporadic GH-secreting tumors. Design: One hundred and fifty-four patients were included in a prospective cohort designed to study the genetic predisposition to GH-secreting tumors together with 270 controls. Methods: In all these subjects, the entire coding sequence of the AIP gene was screened for germline mutations. Results: AIP mutations were detected in 5 out of 154 patients (3%): nonsense mutations in exon 4 (p.Lys201X; n = 2) and in exon 6 (p.Arg304X), one deletion in exon 3 (c.404delA; pHis135LeufsX21), and one mutation affecting the splice acceptor site of exon 4 (c.469-2 A > G). The five patients with an AIP mutation were significantly younger (mean age ± S.D.: 25 ± 10 vs 43 ± 14 years, P = 0.005) and three of them presented with gigantism. One missense mutation (p.Arg304Gln) was found in a single patient that was absent in all controls. Conclusions: Germline mutations of the AIP gene were found in a small proportion of patients with sporadic pituitary somatotropinomas. This study shows that age and gigantism are simple clinical features which can help to select patients for mutation screening. It also supports the role of AIP in pituitary tumorigenesis.

scholarly journals Novel Splice Site Mutation in the PROS1 Gene in a Polish Patient with Venous Thromboembolism: c.602-2delA, Splice Acceptor Site of Exon 7

Medicina ◽  
2020 ◽  
Vol 56 (9) ◽  
pp. 485
Author(s):  
Magdalena Mrożek ◽  
Ewa Wypasek ◽  
Martine Alhenc-Gelas ◽  
Daniel P. Potaczek ◽  
Anetta Undas
Keyword(s):  
Venous Thromboembolism ◽  
Sequence Analysis ◽  
Splice Site ◽  
Splice Site Mutation ◽  
Splice Acceptor Site ◽  
Acceptor Site ◽  
Nucleotide Position ◽  
Splice Acceptor ◽  
Site Mutation ◽  
History Of

We identified a novel splice site mutation of the PROS1 gene in a Polish family with protein S (PS) deficiency and explored the molecular pathogenesis of this previously undescribed variant. A novel mutation was detected in a 26-year-old woman with a history of venous thromboembolism (VTE) provoked by oral contraceptives. Her family history of VTE was positive. The sequence analysis of the PROS1 gene was performed in the proband and the proband’s family. The proband and their asymptomatic father had lower free PS levels (45% and 50%, respectively) and PS activity (48% and 44%, respectively). Total PS levels were normal (65.6% and 62.4%, respectively). The sequence analysis of the PROS1 gene revealed the presence of heterozygous deletion at the nucleotide position c.602-2 in intron 6, just upstream of exon 7, detected in the proband and her father. This variant alters the splice acceptor site of exon 7, and, according to the in silico prediction, it is highly likely to cause in-frame exon 7 skipping. We also presented follow-up data of two other Polish patients with PS deficiency associated with splice site mutations in PROS1 gene.

scholarly journals Giant Intra-Abdominal Desmoid Tumor in a Young Male without History of Surgery, Trauma, or Familial Adenomatous Polyposis

2018 ◽  
Vol 2018 ◽  
pp. 1-5
Author(s):  
Noritoshi Mizuta ◽  
Kozo Tsunemi
Keyword(s):  
Familial Adenomatous Polyposis ◽  
Desmoid Tumor ◽  
Treatment Plan ◽  
Abdominal Cavity ◽  
Beta Catenin ◽  
Desmoid Tumors ◽  
Adenomatous Polyposis ◽  
History Of Surgery ◽  
History Of ◽  
Abdominal Desmoid Tumor

Desmoid tumors are rare, monoclonal myofibroblastic neoplasms that occur in the extremities, the trunk, and the abdominal cavity. We present a case that is significant for its rarity and for consideration of its treatment plan. A 17-year-old male reported swelling of his abdomen and abdominal pain. He was referred to our hospital with no history of surgery, trauma, or familial adenomatous polyposis. A large tumor in the abdominal cavity was detected by computed tomography, and surgical resection was performed. The tumor was thought to have developed from the anterior lobe of the transverse colon mesentery. It weighed 5.9 kg. Tumor cells with collagen fibers were observed in histopathological examination, but heteromorphism and the nuclear fission image were not apparent. Immunostaining revealed beta-catenin expression in the tumor cell nucleus. Diagnosis was an intra-abdominal desmoid tumor. Currently, there are no signs of recurrence. In this case, preoperative diagnosis was difficult, but surgery was the optimal treatment according to the symptoms. Desmoid tumors have invasive development and common local recurrence, so sufficient range of resection including normal tissue and strict follow-up are necessary.

scholarly journals Sirenomelia: two case reports

2021 ◽  
Vol 15 (1) ◽  
Author(s):  
Asiyeh Shojaee ◽  
Firooze Ronnasian ◽  
Mahdiyeh Behnam ◽  
Mansoor Salehi
Keyword(s):  
Case Reports ◽  
Three Dimensional ◽  
First Trimester ◽  
Mendelian Inheritance ◽  
Lower Limbs ◽  
Congenital Deformity ◽  
White Family ◽  
Her Family ◽  
Caudal Regression ◽  
History Of

AbstractBackgroundSirenomelia, also called mermaid syndrome, is a rare lethal multi-system congenital deformity with an incidence of one in 60,000–70,000 pregnancies. Sirenomelia is mainly characterized by the fusion of lower limbs and is widely associated with severe urogenital and gastrointestinal malformations. The presence of a single umbilical artery derived from the vitelline artery is the main anatomical feature distinguishing sirenomelia from caudal regression syndrome. First-trimester diagnosis of this disorder and induced abortion may be the safest medical option. In this report, two cases of sirenomelia that occurred in an white family will be discussed.Case presentationWe report two white cases of sirenomelia occurring in a 31-year-old multigravid pregnant woman. In the first pregnancy (18 weeks of gestation) abortion was performed, but in the third pregnancy (32 weeks) the stillborn baby was delivered by spontaneous vaginal birth. In the second and fourth pregnancies, however, she gave birth to normal babies. Three-dimensional ultrasound imaging showed fusion of the lower limbs. Neither she nor any member of her family had a history of diabetes. In terms of other risk factors, she had no history of exposure to teratogenic agents during her pregnancy. Also, her marriage was non-consanguineous.ConclusionThis report suggests the existence of a genetic background in this mother with a Mendelian inheritance pattern of 50% second-generation incidence in her offspring.

scholarly journals A215 MDR3 DEFICIENCY MIMICKING WILSON DISEASE

2021 ◽  
Vol 4 (Supplement_1) ◽  
pp. 247-248
Author(s):  
M Flanagan ◽  
R Little ◽  
I Siddiqui ◽  
N Jones ◽  
V Ng
Keyword(s):  
Bile Acids ◽  
Wilson Disease ◽  
Genetic Disorder ◽  
Multi Drug Resistance ◽  
Total Serum ◽  
Cholestatic Liver Disease ◽  
Class Iii ◽  
Her Family ◽  
Abcb4 Gene ◽  
History Of

Abstract Background The chronic phenotype of ALF includes a broad differential diagnosis. Class III multi-drug resistance P-glycoprotein 3 (MDR3) deficiency, also referred to as progressive familial intrahepatic cholestasis type 3, is an autosomal recessive genetic disorder. It is caused by a defect on the ABCB4 gene located on chromosome 7, which encodes MDR3. MDR3 is responsible for transporting phosphatidylcholine across the canalicular membrane, thereby allowing it to be incorporated into bile micelles. MDR3 deficiency results in increased levels of free bile acids and detergent bile. Progressive cholangiopathy ensues from this detergent bile and indirectly leads to cholestasis and liver failure in severe cases. Significantly increased urinary and hepatic copper (Cu), which are hallmarks of Wilson disease, have also been reported in patients with acute hepatitis and cholestasis including patients with MDR3 deficiency Aims We report a case of a girl who presented with a chronic phenotype of PALF, who had multiple features of Wilson disease and so was treated as such until genetic analysis confirmed MDR3 deficiency Methods Results A 6 year old girl presented to the ED with a 1mth history of epistaxis and a 1wk history of abdominal pain and distension, facial edema, pallor and fever. Her family history was significant for parental consanguinity and maternal itch during pregnancy. On examination she had clubbing, scleral icterus and a distended abdomen with hepatosplenomegaly. Her bloodwork showed bicytopenia (HGB 53 & Plts 63) along with liver dysfunction (INR 2.9, albumin 25, conjugated bilirubin 9) and raised liver enzymes (transaminases & GGT >10xULN). Her total serum bile acids were raised at 134. An US showed hepatosplenomegaly with multiple hyperechoic nodules and perisplenic varices. She was extensively worked up for malignancy, autoimmune and metabolic disease. Serum ceruloplasmin was reduced, ophthalmology examination showed no KF rings and her 24hr urinary Cu was 10xULN. Liver Cu quantification was markedly raised at 40xULN. Liver biopsy showed cirrhosis with fibrosis related minimal non-specific portal and septal inflammation. Additionally, complete loss of canalicular staining on immunohistochemistry for MDR3 protein was noted, suggestive of MDR3 deficiency. Based on the Cu levels, a provisional diagnosis of Wilson disease was made and Cu chelation therapy was commenced pending genetic testing. A cholestatic gene panel subsequently showed homozygous pathogenic variant for the ABCB4 gene. Trientine was stopped and she was commenced on ursodeoxycholic acid. Though biochemically she remains largely unchanged, she is clinically stable whilst awaiting a liver transplant Conclusions This case highlights the diagnostic difficulties associated with Cu test result interpretation in patients with chronic cholestatic liver disease and urges a thorough consideration of alternative diagnoses of PALF Funding Agencies None

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