Hereditary Cushing’s syndrome caused by primary bilateral macronodular adrenal hyperplasia due to ARMC5 mutation with concomitant primary hyperparathyroidism: the first known case in Russia

Primary bilateral macronodular adrenal hyperplasia (PBMAH), a genetically heterogeneous disease, is a rare cause of Cushings syndrome. Until recently, few cases were attributed to mutations in known genes. However, in 2013, ARMC5, a newly discovered tumor suppressor gene, was identified. Further studies have shown that mutations in the ARMC5 gene are found in 2555% of all PBMAH cases. This article describes a clinical case of hereditary Cushings syndrome caused by PBMAH in a 37-year old patient. The patients family history is remarkable for the presence of Cushings syndrome and PBMAH in the patients mother. Bilateral adrenalectomy was performed as the treatment of choice. Genetic analysis using whole-exome sequencing confirmed the hereditary cause of the disease, revealing a germline heterozygous mutation in the ARMC5 gene. The patient also had concomitant mild primary hyperparathyroidism, which had not been observed before in genetic carriers with the ARMC5 mutation.

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A Novel Mutation in COL4A1 Gene in a Chinese Family with Pontine Autosomal Dominant Microangiopathy and Leukoencephalopathy

Translational Stroke Research ◽

10.1007/s12975-021-00926-0 ◽

2021 ◽

Author(s):

Qing Li ◽

Chengfeng Wang ◽

Wei Li ◽

Zaiqiang Zhang ◽

Shanshan Wang ◽

...

Keyword(s):

Basement Membrane ◽

Skin Biopsy ◽

Exome Sequencing ◽

Whole Exome Sequencing ◽

Autosomal Dominant ◽

Chinese Family ◽

Heterozygous Mutation ◽

Collagen Type Iv ◽

Lacunar Infarcts ◽

Whole Exome

AbstractPontine autosomal dominant microangiopathy and leukoencephalopathy (PADMAL) is a rare hereditary cerebral small vessel disease. We report a novel collagen type IV alpha 1 (COL4A1) gene mutation in a Chinese family with PADMAL. The index case was followed up for 6 years. Neuroimaging, whole-exome sequencing, skin biopsy, and pedigree analysis were performed. She initially presented with minor head injury at age 38. MRI brain showed chronic lacunar infarcts in the pons, left thalamus, and right centrum semiovale. Extensive workup was unremarkable except for a patent foramen ovale (PFO). Despite anticoagulation, PFO closure, and antiplatelet therapy, the patient had recurrent lacunar infarcts in the pons and deep white matter, as well as subcortical microhemorrhages. Whole-exome sequencing demonstrated a novel c.*34G > T mutation in the 3′ untranslated region of COL4A1 gene. Skin biopsy subsequently demonstrated thickening of vascular basement membrane, proliferation of endothelial cells, and stenosis of vascular lumen. Three additional family members had gene testing and 2 of them were found to have the same heterozygous mutation. Of the 18 individuals in the pedigree of 3 generations, 12 had clinical and MRI evidence of PADMAL. The mechanisms of both ischemic and hemorrhagic stroke are likely the overexpression of COLT4A1 in the basement membrane and frugality of the vessel walls. Our findings suggest that the novel c.*34G > T mutation appears to have the same functional consequences as the previously reported COL4A1 gene mutations in patients with PADMAL and multi-infarct dementia of Swedish type.

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Thromboembolism after COVID-19 vaccine in patients with preexisting thrombocytopenia

Cell Death and Disease ◽

10.1038/s41419-021-04058-z ◽

2021 ◽

Vol 12 (8) ◽

Author(s):

Alessandro Mauriello ◽

Manuel Scimeca ◽

Ivano Amelio ◽

Renato Massoud ◽

Antonio Novelli ◽

...

Keyword(s):

Adverse Drug Reaction ◽

Drug Reaction ◽

Exome Sequencing ◽

Clinical Case ◽

Severe Disease ◽

Low Frequency ◽

Postmortem Examination ◽

Capillary Leak ◽

Platelet Factor ◽

Whole Exome

AbstractWhile vaccination is the single most effective intervention to drastically reduce severe disease and death following SARS-CoV-2 infection, as shown in UK and Israel, some serious concerns have been raised for an unusual adverse drug reaction (ADR), including vaccine-induced immune thrombotic thrombocytopenia (VITT) with concurrent low platelets as well as capillary leak syndrome. In fact, the overall safety of the vaccine is highlighted by the low frequency of ADR considering that in UK, by the early June, 40 million first doses and 29 million second doses have been injected; nonetheless, 390 thrombotic events, including 71 fatal events have been reported. Interestingly, the cases reported low platelet counts with the presence of anti-platelet factor-4 (PF4) antibodies, indicating an abnormal clotting reaction. Here, out of three referred cases, we report a post-vaccine clinical case of fatal thrombosis with postmortem examination and whole exome sequencing (WES) analysis, whose pathogenesis appeared associated to a preexisting condition of thrombocytopenia due to myelodysplasia.

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

BMC Medical Genomics ◽

10.1186/s12920-020-00861-3 ◽

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.

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Whole-exome sequencing identifies a novel compound heterozygous mutation of ANKS6 gene in a Chinese nephronophthisis patient

Clinica Chimica Acta ◽

10.1016/j.cca.2019.10.030 ◽

2020 ◽

Vol 501 ◽

pp. 131-135

Author(s):

Boliang Fang ◽

Jun Guo ◽

Chanjuan Hao ◽

Ruolan Guo ◽

Suyun Qian ◽

...

Keyword(s):

Exome Sequencing ◽

Whole Exome Sequencing ◽

Compound Heterozygous Mutation ◽

Heterozygous Mutation ◽

Compound Heterozygous ◽

Whole Exome

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Genetic analysis of impaired trimethylamine metabolism using whole exome sequencing

BMC Medical Genetics ◽

10.1186/s12881-017-0369-8 ◽

2017 ◽

Vol 18 (1) ◽

Cited By ~ 5

Author(s):

Yiran Guo ◽

Liang-Dar Hwang ◽

Jiankang Li ◽

Jason Eades ◽

Chung Wen Yu ◽

...

Keyword(s):

Genetic Analysis ◽

Exome Sequencing ◽

Whole Exome Sequencing ◽

Whole Exome

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Evaluation of whole exome sequencing as an alternative to BeadChip and whole genome sequencing in human population genetic analysis

BMC Genomics ◽

10.1186/s12864-018-5168-x ◽

2018 ◽

Vol 19 (1) ◽

Cited By ~ 2

Author(s):

Zoltán Maróti ◽

Zsolt Boldogkői ◽

Dóra Tombácz ◽

Michael Snyder ◽

Tibor Kalmár

Keyword(s):

Genetic Analysis ◽

Whole Genome Sequencing ◽

Exome Sequencing ◽

Whole Exome Sequencing ◽

Genome Sequencing ◽

Population Genetic ◽

Human Population ◽

Whole Genome ◽

Population Genetic Analysis ◽

Whole Exome

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Genetic analysis of parathyroid and pancreatic tumors in a patient with multiple endocrine neoplasia type 1 using whole-exome sequencing

BMC Medical Genetics ◽

10.1186/s12881-017-0465-9 ◽

2017 ◽

Vol 18 (1) ◽

Cited By ~ 5

Author(s):

Bo-Young Kim ◽

Mi-Hyun Park ◽

Hae-Mi Woo ◽

Hye-Yeong Jo ◽

Ji Hoon Kim ◽

...

Keyword(s):

Genetic Analysis ◽

Exome Sequencing ◽

Whole Exome Sequencing ◽

Multiple Endocrine Neoplasia ◽

Multiple Endocrine Neoplasia Type ◽

Pancreatic Tumors ◽

Endocrine Neoplasia ◽

Endocrine Neoplasia Type ◽

Whole Exome

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Abstract 16468: Results of Research Genetic Testing in Pediatric Cardiomyopathy Patients Justify Broader Clinical Genetic Testing

Circulation ◽

10.1161/circ.132.suppl_3.16468 ◽

2015 ◽

Vol 132 (suppl_3) ◽

Author(s):

Stephanie M Ware ◽

Steven E Lipshultz ◽

Steven D Colan ◽

Ling Shi ◽

Charles E Canter ◽

...

Keyword(s):

Genetic Testing ◽

Family History ◽

Risk Stratification ◽

Exome Sequencing ◽

Whole Exome Sequencing ◽

Clinical Genetic ◽

Clinical Genetic Testing ◽

Whole Exome ◽

Pediatric Cardiomyopathy ◽

History Of

Introduction: Pediatric cardiomyopathies are genetically heterogeneous diseases with high risk of death or cardiac transplant. Despite progress in identifying causes, the majority of cases remain idiopathic. Currrently, genetic testing is not performed in all children with cardiomyopathy. Gene identification leads to better individual risk stratification and has the potential to stimulate the development of therapies based on the underlying mutation. The aim of this study is to identify genetic mutations in pediatric cardiomyopathy patients using whole exome sequencing. Hypothesis: Sarcomeric mutations are under-diagnosed causes of all forms of cardiomyopathy in children. Methods: Probands with cardiomyopathy were recruited from 11 institutions. Results of clinical genetic testing prior to enrollment were collected. Whole exome sequencing was performed and mutations were identified in 35 genes currently available on clinical genetic testing panels. Results: The initial 154 probands subjected to exome included 78 patients with DCM, 43 with HCM, 14 with RCM, and 19 with LVNC, mixed, or unknown types. Familial disease was present in 38% and the remainder were idiopathic. Twenty-seven percent had positive clinical genetic testing prior to enrollment. Exome testing identified mutations in 38 subjects who had not had clinical testing, increasing the cohort positive testing rate to 55% (DCM, 34.6%; HCM, 74.4%; RCM, 71.4%). Forty-five percent of subjects with no family history of disease had an identifiable mutation. Conclusions: Pediatric cardiomyopathy patients have a high incidence of mutations that can be identified by clinically available genetic testing. Lack of a family history of cardiomyopathy was not predictive of normal genetic testing. These results support the broader use of genetic testing in pediatric patients with all functional phenotypes of cardiomyopathy to identify disease causation allowing better family risk stratification.

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