Germline variants of the MEN1 gene in 132 subjects with clinical indication of genetic diagnosis, born in Argentina

2021 ◽  
Author(s):  
Fainstein-Day Patricia ◽  
Viale Maria Lorena ◽  
Serra Maria Pia ◽  
Andrea Kozak
Keyword(s):  
Genetic Diagnosis ◽  
Clinical Indication ◽  
Germline Variants ◽  
Men1 Gene

scholarly journals Preimplantation Genetic Testing for Kidney Disease-Related Genes: A Laboratory’s Experience

2021 ◽  
Vol 52 (8) ◽  
pp. 684-690
Author(s):  
Jessica L. Chaperon ◽  
Nina M. Wemmer ◽  
Trudy A. McKanna ◽  
Dinah M. Clark ◽  
Maggie A. Westemeyer ◽  
...  
Keyword(s):  
Genetic Testing ◽  
Kidney Disease ◽  
Molecular Genetic ◽  
Genetic Diagnosis ◽  
Clinical Indication ◽  
Common Disease ◽  
Reference Laboratory ◽  
Preimplantation Genetic Testing ◽  
Kidney Involvement ◽  
Molecular Genetic Diagnosis

<b><i>Introduction:</i></b> Recent literature highlights the clinical utility of genetic testing for patients with kidney disease. Genetic testing provides significant benefits for reproductive risk counseling, including the option of in vitro fertilization with preimplantation genetic testing for monogenic disease (PGT-M). PGT-M allows for a significant reduction in risk for a pregnancy affected with the familial disease. We aim to summarize our experience with PGT-M for genes with kidney involvement as either a primary or secondary feature of the disease. <b><i>Methods:</i></b> All PGT-M tests performed by the reference laboratory between September 2010 and July 2020 were reviewed for clinical indication and cases for which the disease tested included a renal component. Each patient referred for PGT-M had an existing molecular genetic diagnosis themselves or in their family. Frequency of each condition, gene, inheritance pattern, and year over year increase in referral cases was analyzed. <b><i>Results:</i></b> In the study cohort, the most common disease targeted was autosomal dominant polycystic kidney disease, caused by pathogenic variants in the <i>PKD1</i> or <i>PKD2</i> genes, which accounted for 16.5% (64/389) of cases. The 5 most common referral indications accounted for 51.9% (202/389) of the cases. Autosomal recessive inheritance accounted for 52.0% (26/50) of conditions for which PGT-M was performed. The number of PGT-M tests performed for conditions that included either primary or secondary kidney disease increased from 5 cases in 2010 to 47 cases in the 2020 study period. <b><i>Discussion/Conclusion:</i></b> These data suggest that the pursuit of PGT-M by couples at risk for passing on conditions with a kidney component is common and has significantly increased since 2010. With this rising trend of patients undergoing PGT-M and the prerequisite of molecular genetic confirmation in the PGT-M process, this study underscores the importance of the reproductive component to a molecular genetic diagnosis for patients with kidney disease, especially as the accessibility of genetic testing and utilization by nephrologists grows.

scholarly journals Identification of Novel Variants in MEN1: A Study Conducted with Four Multiple Endocrine Neoplasia Type 1 Patients

2020 ◽  
Vol 52 (11) ◽  
pp. 788-795
Author(s):  
Wen-mu Hu ◽  
Qin Zhang ◽  
Li-hua Huang ◽  
Zhao-hui Mo ◽  
Xiao-dan Long ◽  
...  
Keyword(s):  
Multiple Endocrine Neoplasia ◽  
Multiple Endocrine Neoplasia Type ◽  
Genetic Characteristics ◽  
Germline Variants ◽  
Men1 Gene ◽  
Endocrine Neoplasia ◽  
Endocrine Neoplasia Type ◽  
Novel Variants ◽  
The Impact

AbstractMultiple endocrine neoplasia type 1 (MEN1) is an autosomal dominant inherited endocrine tumor syndrome caused by inactivating variants of the MEN1 gene. The aim of this study is to explore the clinical and genetic characteristics of four MEN1 patients. We isolated genomic deoxyribonucleic acid from lymphocytes, parathyroid, and thymic tumoral tissue specimens from the MEN1 patients. All exons of the MEN1 and CDNK1B genes and adjacent exon-intron sequences were amplified by polymerase chain reaction and subsequently sequenced. Further, the splice alterations were studied by sequencing the amplified RT-PCR products for MEN1 cDNA. We identified four heterozygous MEN1 germline variants: c.564delC, c.1268G>A, IVS5+5delG, and c.1546_1547insC. Both c.564delC and IVS5+5delG were novel variants. The impact of the MEN1 splice variant, IVS5+5delG, was evaluated using bioinformatics and in vitro analyses. The analyses indicated that this variant resulted in skipping of the neighboring exon and was disease-causing. Two novel somatic variants, c.249_252delGTCT and c.313_314insC, were found. Additionally, loss of heterozygosity (LOH) for the MEN1 locus (IVS5+5delG and c.564delC) was found in tumor tissue samples from the MEN1 patients, consistent with Knudson’s two-hit mechanism. We identified four MEN1 germline variants and two novel somatic variants. Early recognition of the phenotype coupled with variant screening of the MEN1 gene is the key to diagnosing and treating MEN1 effectively at an early stage.

Current concepts of the interventional treatment of proximal supraaortic vessel stenosis

VASA ◽  
2012 ◽  
Vol 41 (5) ◽  
pp. 313-318 ◽  
Author(s):  
Ernemann ◽  
Bender ◽  
Melms ◽  
Brechtel ◽  
Kobba ◽  
...  
Keyword(s):  
Treatment Strategies ◽  
Carotid Bifurcation ◽  
Current Treatment ◽  
Long Term Results ◽  
Clinical Indication ◽  
Interventional Treatment ◽  
Special Focus ◽  
Brachiocephalic Artery ◽  
Treatment Concepts ◽  
Angioplasty And Stenting

Interventional therapies using angioplasty and stenting of symptomatic stenosis of the proximal supraaortic vessels have evolved as safe and effective treatment strategies. The aim of this paper is to summarize the current treatment concepts for stenosis in the subclavian and brachiocephalic artery with regard to clinical indication, interventional technique including selection of the appropriate vascular approach and type of stent, angiographic and clinical short-term and long-term results and follow-up. The role of hybrid interventions for tandem stenoses of the carotid bifurcation and brachiocephalic artery is analysed. A systematic review of data for angioplasty and stenting of symptomatic extracranial vertebral artery stenosis is discussed with a special focus on restenosis rate.

Increased enquiries for preimplantation genetic diagnosis (PGD)

2014 ◽  
Vol 74 (S 01) ◽  
Author(s):  
KJ Heiliger ◽  
D Gutknecht ◽  
C Adelfalk ◽  
A Eder ◽  
M Bals-Pratsch ◽  
...  
Keyword(s):  
Preimplantation Genetic Diagnosis ◽  
Genetic Diagnosis

Treatment of maternal hyperthyroidism with antithyroid agents and changes in thyrotrophin and thyroxine in the newborn

1981 ◽  
Vol 97 (2) ◽  
pp. 186-195 ◽  
Author(s):  
B.-A. Lamberg ◽  
E. Ikonen ◽  
K. Teramo ◽  
G. Wägar ◽  
K. Österlund ◽  
...  
Keyword(s):  
Laboratory Test ◽  
Cord Blood ◽  
Pregnant Women ◽  
Newborn Infants ◽  
Antithyroid Drug ◽  
Clinical Indication ◽  
Antithyroid Drugs ◽  
Serum Thyroxine ◽  
Antithyroid Agents ◽  
Serum Tsh

Abstract. Eleven pregnant women with concomitant hyperthyroidism were treated with antithyroid drugs. At monthly intervals serum thyroxine (T4) and triiodothyronine (T3) were measured with radioimmunoassay, the Sephadex uptake of radioactive triiodothyronine (T3U) determined and the free T4 and T3 indices calculated (FT4I, FT3I). TSH-binding inhibiting immunoglobulins (TBII) were determined by the radiomembrane assay. Serum TSH and T4 were measured at delivery from cord blood and/or from the newborn infants some days after birth. Serum TSH was significantly elevated in one infant. There was an inadequate post-partal rise in serum T4 concentration in this child and in another who showed only a marginal elevation of TSH. The mothers of these infants were given carbimazole in doses of 30 and 25 mg/day, respectively, at the time of delivery. No significant changes were seen in other infants, the daily doses being 20 mg of carbimazole or less. There was no clinical indication of hypo- or hyperthyroidism in any of the newborn. The TBII were positive in most patients and there was a trend of normalization during treatment. No relationship between the dose of antithyroid drug and the level of TBII could be seen. During treatment the dose was adjusted according to the FT3I values. This seems to be an adequate laboratory test for this purpose.

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