Atypical ADPKD Due to a Pathogenic Variant: An Educational Case Report.

Rationale: Due to next-generation sequencing, variants in new genes such as are recently being identified as causing atypical autosomal dominant polycystic kidney disease (ADPKD). It is important to describe phenotypes associated with these variants in order to increase awareness among clinicians, especially since genetic variability affects ADPKD severity.

Presenting Concerns Of The Patient: We describe a 55-year-old female patient of Haitian origin who presented with slowly deteriorating kidney function, microscopic hematuria, proteinuria, enlarged kidneys with innumerable small cysts, and a family history of chronic kidney disease and cysts.

Molecular Genetic Characteristics of , a Proposed New Ovarian Cancer Predisposing Gene.

was recently identified as a new candidate ovarian cancer (OC)-predisposing gene from the genetic analysis of carriers of c.1813C>T; p.L605F in OC families.

A comparative analysis of RAS variants in patients with disorders of somatic mosaicism.

Purpose: RAS genes (HRAS, KRAS, and NRAS) are commonly found to be mutated in cancers, and activating RAS variants are also found in disorders of somatic mosaicism (DoSM). A survey of the mutational spectrum of RAS variants in DoSM has not been performed.

Methods: A total of 938 individuals with suspected DoSM underwent high-sensitivity clinical next-generation sequencing-based testing.

Amyloid Deposits in a Functionally Unicuspid Stenotic Aortic Valve.

Amyloidosis concomitant to aortic stenosis usually occurs with myocardial infiltration by the transthyretin protein. To our knowledge, this is the first report of localized amyloidosis of indeterminate type in a severely calcified and functionally unicuspid aortic valve. Isolated dystrophic valvular amyloidosis is believed to be related to fibrocalcific valve disease.

Genetic Dissection of Primary Aldosteronism in a Patient With MEN1 and Ipsilateral Adrenocortical Carcinoma and Adenoma.

Background: Adrenal tumors are found in up to 40% of patients with multiple endocrine neoplasia type 1 (MEN1). However, adrenocortical carcinomas (ACC) and primary aldosteronism (PA) are rare in MEN1.

Case: A 48-year-old woman known to have primary hyperparathyroidism and hypertension with hypokalemia was referred for a right complex 8-cm adrenal mass with a 38.

Case Review: Whole-Exome Sequencing Analyses Identify Carriers of a Known Likely Pathogenic Intronic Variant in Ovarian Cancer Cases Clinically Negative for Pathogenic and Variants.

Background: Detecting pathogenic intronic variants resulting in aberrant splicing remains a challenge in routine genetic testing. We describe germline whole-exome sequencing (WES) analyses and apply in silico predictive tools of familial ovarian cancer (OC) cases reported clinically negative for pathogenic BRCA1 and BRCA2 variants. Methods: WES data from 27 familial OC cases reported clinically negative for pathogenic BRCA1 and BRCA2 variants and 53 sporadic early-onset OC cases were analyzed for pathogenic variants in BRCA1 or BRCA2.

A decade of RAD51C and RAD51D germline variants in cancer.

Defects in DNA repair genes have been extensively associated with cancer susceptibility. Germline pathogenic variants (GPV) in genes involved in homologous recombination repair pathways predispose to cancers arising mainly in the breast and ovary, but also other tissues. The RAD51 paralogs RAD51C and RAD51D were included in this group 10 years ago when germline variants were associated with non-BRCA1/2 familial ovarian cancer.

A functionally impaired missense variant identified in French Canadian families implicates FANCI as a candidate ovarian cancer-predisposing gene.

Background: Familial ovarian cancer (OC) cases not harbouring pathogenic variants in either of the BRCA1 and BRCA2 OC-predisposing genes, which function in homologous recombination (HR) of DNA, could involve pathogenic variants in other DNA repair pathway genes.

Methods: Whole exome sequencing was used to identify rare variants in HR genes in a BRCA1 and BRCA2 pathogenic variant negative OC family of French Canadian (FC) ancestry, a population exhibiting genetic drift. OC cases and cancer-free individuals from FC and non-FC populations were investigated for carrier frequency of FANCI c.

Current gene panels account for nearly all homologous recombination repair-associated multiple-case breast cancer families.

It was hypothesized that variants in underexplored homologous recombination repair (HR) genes could explain unsolved multiple-case breast cancer (BC) families. We investigated HR deficiency (HRD)-associated mutational signatures and second hits in tumor DNA from familial BC cases. No candidates genes were associated with HRD in 38 probands previously tested negative with gene panels.

Whether, when, how, and how much? General public's and cancer patients' views about the disclosure of genomic secondary findings.

Background: Data on the modalities of disclosing genomic secondary findings (SFs) remain scarce. We explore cancer patients' and the general public's perspectives about disclosing genomic SFs and the modalities of such disclosure.

Methods: Sixty-one cancer patients (n = 29) and members of the public (n = 32) participated in eight focus groups in Montreal and Quebec City, Canada.

Small adrenal incidentaloma becoming an aggressive adrenocortical carcinoma in a patient carrying a germline APC variant.

Purpose: Recent guidelines on adrenal incidentalomas suggested in patients with an indeterminate adrenal mass and no significant hormone excess that follow up with a repeat noncontrast CT or MRI after 6-12 months may be an option.

Methods: We report the case of a 32-year-old woman who presented with a 2.9 × 1.

Langerhans cell histiocytosis presenting as Crohn's disease: a case report.

Purpose: We describe an exceptional case of Langerhans cell histiocytosis (LCH) that presented as Crohn's disease and primary sclerosing cholangitis.

Methods: The patient's clinical, endoscopic, and histologic data from the Centre Hospitalier de l'Universite de Montreal were reviewed, as well as the literature on LCH involving the digestive tract and the liver, with a focus on the similarities with Crohn's disease and primary sclerosing cholangitis.

Results: A 39 years-old man first presented with anal fissures and deep punctiform colonic ulcers.

Clinical follow-up and breast and ovarian cancer screening of true BRCA1/2 noncarriers: a qualitative investigation.

Purpose: Most women from BRCA1/2 mutation-positive families who did not inherit the familial mutation have breast and ovarian cancer risks similar to those of women of the same age in the general population. However, recent studies suggest that some of these noncarriers may exhibit screening practices that may be considered as excessive compared to general population screening guidelines. Reasons for such tendencies remain largely unknown.