EPAS1-related pheochromocytoma/paraganglioma.

In 2012, somatic EPAS1 pathogenic variants were found to cause a triad of pheochromocytoma/paragangliomas (PPGLs), polycythemia, and somatostatinoma. Since then, a limited number of studies on this subject have been reported, and data on the long-term outcome of metastatic disease are not available on this rare syndrome. We comprehensively reviewed EPAS1-related PPGL and describe an unusual patient who has been living with an EPAS1-related metastatic PPGL for 47 years.

LncRNA GAS8-AS1 dinucleotide genetic variant is associated with early-stage disease, lymph node, and distant metastasis in differentiated thyroid cancer.

Purpose: Long noncoding RNAs (lncRNAs) play an essential role in the epigenetic regulation of various key genes involved in vital cellular functions. A somatic dinucleotide mutation in the lncRNA GAS8-AS1 was reported in Chinese papillary thyroid cancer. However, GAS8-AS1 dinucleotide alteration and its impact have never been explored in differentiated thyroid cancers and other populations.

An aggressive cabergoline-resistant, temozolomide-responsive macroprolactinoma due to a germline pathogenic variant in the absence of paraganglioma or pheochromocytoma.

Context: Germline succinate dehydrogenase subunit B () pathogenic variants are characteristic of familial paraganglioma (PGL) syndrome type 4. This syndrome frequently presents with abdominal PGL and has high tendency for locally aggressive behavior and distant metastasis. The vast majority of pituitary adenomas (PAs) are sporadic.

Expanding the phenotypic and genotypic spectrum of GGPS1 related congenital muscular dystrophy.

Congenital muscular dystrophies are a group of progressive disorders with wide range of symptoms associated with diverse cellular mechanisms. Recently, biallelic variants in GGPS1 were linked to a distinct autosomal recessive form of muscular dystrophy associated with hearing loss and ovarian insufficiency. In this report, we present a case of a young patient with a homozygous variant in GGPS1.

Thyroid Cancer, Neuroendocrine Tumor, Adrenal Adenoma, and Other Tumors in a Patient With a Germline Mutation.

Context: Multiple tumors in the same patient suggest a genetic predisposition. Here, we report a patient who presented with several unusual types of malignant and benign tumors, presumably due to a pathogenic germline mutation.

Case: A 69-year-old woman presented with a 2-year history of abdominal pain and diarrhea.

Molecular Genetics of Diffuse Sclerosing Papillary Thyroid Cancer.

Context: Diffuse sclerosing papillary thyroid cancer (DSPTC) is rare, with limited data on its molecular genetics.

Objective: We studied the molecular genetics of a cohort of DSPTC.

Methods: DNA was isolated from paraffin blocks of 22 patients with DSPTC (15 females, 7 males, median age 18 years, range 8-81).

A molecular study of pediatric pilomyxoid and pilocytic astrocytomas: Genome-wide copy number screening, retrospective analysis of clinicopathological features and long-term clinical outcome.

Background: Pilocytic Astrocytoma (PA) is the most common pediatric brain tumors. PAs are slow-growing tumors with high survival rates. However, a distinct subgroup of tumors defined as pilomyxoid astrocytoma (PMA) presents unique histological characteristics and have more aggressive clinical course.

The impact of thyroid imaging reporting and data system on the management of Bethesda III thyroid nodules.

Objectives: Atypia of undetermined significance (AUS) or follicular lesion of undetermined significance (FLUS) is a heterogeneous category of fine needle aspiration cytology (FNAC); the management of this condition remains controversial. The clinical significance of such patients relies on the exclusion of malignancy. In this study, we aimed to determine the validity of the American College of Radiology Thyroid Imaging Reporting and Data System (ACR TI-RADS) (2017) for predicting malignancy in this specific category of patients.

Clinicopathologic and genomic characterizations of brain metastases using a comprehensive genomic panel.

Central nervous system (CNS) metastasis is the most common brain tumor type in adults. Compared to their primary tumors, these metastases undergo a variety of genetic changes to be able to survive and thrive in the complex tissue microenvironment of the brain. In clinical settings, the majority of traditional chemotherapies have shown limited efficacy against CNS metastases.

A Unique Mechanism of a Novel Synonymous PHEX Variant Causing X-Linked Hypophosphatemia.

Context: Synonymous mutations are usually nonpathogenic.

Objective: We report here a family with X-linked hypophosphatemia (XLH) due to a novel synonymous PHEX variant with a unique mechanism.

Methods: We studied a 4-member family (a mother, a son, and 2 daughters), all affected with XLH.

Case Report: Severe Gonadal Dysgenesis Causing 46,XY Disorder of Sex Development Due to a Novel Variant.

Mutations in the nuclear receptor subfamily 5 group A member 1 () are the underlying cause of 10-20% of 46,XY disorders of sex development (DSDs). We describe a young girl with 46,XY DSD due to a unique novel mutation of the gene. An 11-year-old subject, raised as a female, was noticed to have clitromegly.

Fumarate Hydratase is a Novel Gene for Familial Non-Medullary Thyroid Cancer.

Context: The majority of cases of epithelial cell-derived thyroid cancer are sporadic. Familial non-medullary thyroid cancer (FNMTC) occurs in about 5% to 9% of cases, either as a part of known syndromes such as Cowden syndrome or in the form of familial clustering of 2 or more affected family members. Hereditary leiomyoma and renal cell cancer (HLRCC) syndrome is a rare familial cancer syndrome.

Papillary Thyroid Cancer and a Promotor Mutation-positive Paraganglioma in a Patient With a Germline Mutation.

Purpose: About 40% of paragangliomas (PGL) are due to germline mutations in one of several susceptibility genes. These genes rarely predispose to other non-PGL tumors. Here, we describe and functionally characterize a germline mutation in a patient who developed a mutation-positive papillary thyroid cancer (PTC) and a promotor mutation-positive PGL.

Clinical, Neurophysiological, Radiological, Pathological, and Genetic Features of Dysferlinopathy in Saudi Arabia.

Background: To characterize the phenotypic, neurophysiological, radiological, pathological, and genetic profile of 33 Saudi Arabian families with dysferlinopathy.

Methods: A descriptive observational study was done on a cohort of 112 Saudi Arabian families with LGMD. Screening for the Dysferlin (DYSF) gene was done in a tertiary care referral hospital in Saudi Arabia.

Phenotypic Variability of Variants Causing Congenital Myopathy: Report of Two Unrelated Patients from a Highly Consanguineous Population.

Congenital myopathies are rare neuromuscular hereditary disorders that manifest at birth or during infancy and usually appear with muscle weakness and hypotonia. One of such disorders, early-onset myopathy, areflexia, respiratory distress, and dysphagia (EMARDD, OMIM: 614399, MIM: 612453), is a rare autosomal recessive disorder caused by biallelic mutations (at homozygous or compound heterozygous status) in (multiple epidermal growth factor-like domains protein family). Here, we report two unrelated patients, who were born to consanguineous parents, having two novel deleterious variants.

Controversy on the management of patients carrying RET p.V804M mutation.

Context: RET p.V804M is classified as a moderate risk mutation for familial medullary thyroid cancer (FMTC). There is a significant controversy on the management of patients carrying this mutation.

Analysis of and somatic mutations in differentiated thyroid cancers.

Anaplastic lymphoma kinase (), isocitrate dehydrogenase 1 and 2 ( and ) and matrix metalloproteinase 8 () gene mutations have been frequently reported in human cancers; however, to the best of our knowledge, they have not been specifically examined in differentiated thyroid cancers (DTCs). Therefore, the present study aimed to determine the somatic mutational frequencies of these genes in DTCs. Mutational analysis of the (exons 23, 24 and 25), (exon 4), (exon 4), and (all exons 1-10) was performed in 126, 271, 271 and 50 DTCs, respectively.

MYH1 is a candidate gene for recurrent rhabdomyolysis in humans.

Rhabdomyolysis is a serious medical condition characterized by muscle injury, and there are recognized genetic causes especially in recurrent forms. The majority of these cases, however, remain unexplained. Here, we describe a patient with recurrent rhabdomyolysis in whom extensive clinical testing failed to identify a likely etiology.

Single nucleotide polymorphisms in matrix metalloproteinase 2 (MMP2) enhance BRAFV600E mutation-mediated oncogenicity and invasiveness of papillary thyroid cancer cells.

Thyroid cancer is a common endocrine neoplasm. Despite its good prognosis, it can lead to significant morbidity and mortality due to metastasis and recurrence. However, the factors involved in metastasis are not well studied.

Angiocentric glioma of brainstem.

Angiocentric glioma is a rare brain tumor commonly found in frontal or temporal lobes. It has a benign course, and surgical resection can be curative. Brainstem location is extremely rare, with only six cases reported so far in the literature.

One genotype, many phenotypes: SDHB p.R90X mutation-associated paragangliomas.

Context: SDHB p.R90X germline mutation is the most common genetic alteration in our patients with familial or apparently sporadic pheochromocytoma/paraganglioma (PPGL).

Objective: To analyze the clinical and pathological characteristics, response to therapy, and outcome of patients with SDHB p.

Genetic Alterations in Pediatric Thyroid Cancer Using a Comprehensive Childhood Cancer Gene Panel.

Context: Pediatric differentiated thyroid cancer (DTC) differs from adult DTC in its underlying genetics and clinicopathological features. In this report, we studied these aspects in 48 cases of pediatric DTC.

Patients And Methods: We used the comprehensive Oncomine Childhood Cancer Gene panel on Ion Torrent next-generation sequencing platform.

Infantile atypical subependymal giant cell astrocytoma.

Subependymal giant cell astrocytoma is a benign WHO grade I intraventricular tumor arise in patients with tuberous sclerosis complex. Previous reported described histopathological predictors of more aggressive forms, terms atypical SEGA in infantile age group. Other reports showed possible transformation of SEGA into glioblastoma, or misdiagnosis as glioblastoma due to the presence of atypical histopathological features.

Mutational profile and genotype/phenotype correlation of non-familial pheochromocytoma and paraganglioma.

About 30%-40% of patients with pheochromocytoma (PCC) and paraganglioma (PGL) have underlying germline mutations in certain susceptibility genes despite absent family history of these tumors. Here, we present mutational profile of 101 such patients with PCC/PGL (PPGL) from the highly consanguineous population of Saudi Arabia. Of 101 cases with PPGL, 37/101 (36.

GPCR-mediated PI3K pathway mutations in pediatric and adult thyroid cancer.

Whole exome sequencing (WES) recently identified frequent mutations in the genes of GPCR-mediated PI3K pathway (, , and ) in a Chinese population with papillary thyroid cancers (PTCs). The study found mutations as novel gene mutations in adult population with differentiated thyroid cancer (DTC). Here, we determine the prevalence of somatic mutations in this pathway ( (exon 1), (exons 9 and 20) and (exons 5, 6, 7 and 8) in 323 thyroid samples consisting of 17 multinodular goiters (MNG), 89 pediatric DTCs, 204 adult DTCs, and 13 aggressive thyroid cancers including 10 poorly differentiated (PDTC) and 3 anaplastic thyroid cancer (ATC) from another ethnic population.