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 Molecular Genetic Diagnosis of Omani Patients With Inherited Cystic Kidney Disease

2019 ◽  
Vol 4 (12) ◽  
pp. 1751-1759 ◽  
Author(s):  
Intisar Al Alawi ◽  
Issa Al Salmi ◽  
Fatma Al Rahbi ◽  
Mohamed Al Riyami ◽  
Naifain Al Kalbani ◽  
...  
Keyword(s):  
Kidney Disease ◽  
Molecular Genetic ◽  
Genetic Diagnosis ◽  
Cystic Kidney Disease ◽  
Cystic Kidney ◽  
Molecular Genetic Diagnosis

Autosomal dominant tubule-interstitial kidney disease, including medullary cystic disease

2018 ◽  
Author(s):  
John A. Sayer
Keyword(s):  
Kidney Disease ◽  
Autosomal Dominant ◽  
Molecular Genetic ◽  
Genetic Diagnosis ◽  
Cystic Kidney Disease ◽  
Cystic Kidney ◽  
Molecular Genetic Diagnosis ◽  
End Stage

The term medullary cystic kidney disease (MCKD) describes a group of autosomal dominantly inherited renal disorders. The term MCKD is used interchangeably with other terms, most commonly autosomal dominant interstitial kidney disease, and now may be distinguished using a molecular genetic diagnosis into at least three types. These include MCKD type 1, MCKD type 2 (also known now as uromodulin-associated kidney disease), and REN-associated kidney disease. Each of these types have phenotypic overlap but with a few distinguishing features. MCKD typically leads to end-stage renal failure between 30 and 70 years of age. Extrarenal features may include gout and childhood anaemia.

Clinical and genetic investigation of 136 Japanese patients with congenital hypothyroidism

2020 ◽  
Vol 33 (6) ◽  
pp. 691-701 ◽  
Author(s):  
Tatsushi Tanaka ◽  
Kohei Aoyama ◽  
Atsushi Suzuki ◽  
Shinji Saitoh ◽  
Haruo Mizuno
Keyword(s):  
Congenital Hypothyroidism ◽  
Molecular Genetic ◽  
Genetic Diagnosis ◽  
Japanese Patients ◽  
Thyroid Stimulating Hormone ◽  
Allelic Variant ◽  
Genetic Investigation ◽  
Pathogenic Variants ◽  
Recessive Genes ◽  
Molecular Genetic Diagnosis

AbstractObjectivesCongenital hypothyroidism (CH) is the most common congenital endocrine disorder. Recent advances in genetic testing have revealed its causative mutations in some CH patients. However, the underlying etiology remains unknown in most patients. This study aimed to perform clinical and genetic investigation in Japanese CH patients to uncover genotype-phenotype correlations.MethodsWe enrolled 136 Japanese patients with transient or permanent CH between April 2015 and March 2017, and performed next-generation sequencing of 19 genes implicated in CH.ResultsWe identified potentially pathogenic bi-allelic variants in DUOX2, TSHR, and TPO in 19, 5, and 1 patient, respectively (autosomal recessive), and a potentially pathogenic mono-allelic variant in NKX2-1 (autosomal dominant) in 1 patient. Molecular genetic diagnosis was highly suggested in 26 patients (19%) from 23 families. We also detected a potentially pathogenic mono-allelic variant in five recessive genes (DUOX2, TSHR, TG, DUOXA2, and TPO) in 31 unrelated patients (23%), although the pathogenicity of these variants remains inconclusive. Patients with bi-allelic DUOX2 variants showed a more severe clinical presentation in infancy than those with bi-allelic TSHR variants. However, this trend reversed beyond infancy. There were no statistical differences in initial thyroid stimulating hormone, free thyroxine, thyroglobulin, and levothyroxine dose as of March 2017 between patients with bi-allelic and mono-allelic DUOX2 variants.ConclusionsThe prevalence of potentially-pathogenic variants in Japanese CH patients was similar to that found by previous reports. Our study demonstrates a genotype-phenotype correlation in Japanese CH patients.

Mitochondrial encephalopathies: molecular genetic diagnosis from blood samples

The Lancet ◽  
1991 ◽  
Vol 337 (8753) ◽  
pp. 1311-1313 ◽  
Author(s):  
S.R. Hammans ◽  
M.G. Sweeney ◽  
M. Brockington ◽  
J.A. Morgan-Hughes ◽  
A.E. Harding
Keyword(s):  
Molecular Genetic ◽  
Genetic Diagnosis ◽  
Blood Samples ◽  
Molecular Genetic Diagnosis

scholarly journals Clinician's modern approaches to molecular genetic diagnosis of glioblastomas

2021 ◽  
Vol 67 (1) ◽  
pp. 13-19
Author(s):  
Turna Ashkhatcava ◽  
Marina Tatarinova ◽  
Lali Kogoniya ◽  
David Naskhletashvili ◽  
Vadim Zhukov
Keyword(s):  
Braf Mutation ◽  
Molecular Mechanisms ◽  
Molecular Genetic ◽  
Genetic Diagnosis ◽  
Braf V600e ◽  
Poor Prognostic Factor ◽  
Molecular Genetic Diagnosis ◽  
The Brain ◽  
Tert Mutation ◽  
Primary Glioblastomas

The article is devoted to the issue of molecular genetic diagnosis of cerebral glioblastomas. Despite significant advances in neurooncology, little progress has been made in prolonging the life of patients with cerebral glioblastoma, and a significant part of the effectiveness of treatment depends on the recognition of two prognostic biomarkers: mutations of the isocitrate dehydrogenase (IDH) promoter and  the methylation of the O6-methylguanine methyl transferase (MGMT) promoter. The article summarizes the data of world and domestic clinical studies, allowing to supplement the histological characteristics of primary glioblastomas with genetic markers: the presence of the TERT mutation, EFGR amplification, loss of PTEN function, LOH 10q, and the presence of the BRAF mutation. It should be noted that the amplification of EGFR, causing resistance to apoptotic stimuli and alkylating chemotherapy with Temozolomide, attracts much attention as a therapeutic target. The frequency of occurrence of the TERT mutation is 90% of all tumors of various genesis, most often the TERT mutation is found in oligodendroglioma or primary glioblastoma. Loss of heterozygosity in the region of localization of the PTEN gene is observed in many types of sporadic tumors, including more than 40% of glioblastomas. Mutations in this gene are found in tumors of the brain, endometrium, prostate, kidney, and mammary gland. The presence of a PTEN mutation is a poor prognostic factor. LOH 22q is much more common in secondary glioblastomas (82%) than in primary glioblastomas (41%). Among brain tumors, the BRAF mutation is most common with pleomorphic xanastrocytoma (60-70%).The BRAF V600E mutation was found in epithelioid glioblastoma, which is a rare and aggressive type of glioblastoma, characterized by an unfavorable prognosis (about 6 months) and frequent leptomeningeal spread. Thus, knowledge of the molecular mechanisms of carcinogenesis will enable a personalized approach to treatment with glioblastomas of the brain.

scholarly journals Molecular Genetic Diagnosis of von Hippel-Lindau Disease: Analysis of Five Japanese Families

1996 ◽  
Vol 87 (5) ◽  
pp. 423-428 ◽  
Author(s):  
Hiroshi Kanno ◽  
Taro Shuin ◽  
Keiichi Kondo ◽  
Susumu Ito ◽  
Masahiko Hosaka ◽  
...  
Keyword(s):  
Molecular Genetic ◽  
Genetic Diagnosis ◽  
Von Hippel Lindau ◽  
Von Hippel Lindau Disease ◽  
Molecular Genetic Diagnosis ◽  
Disease Analysis
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