scholarly journals A second hit somatic (p.R905W) and a novel germline intron-mutation of TSC2 gene is found in intestinal lymphangioleiomyomatosis: a case report with literature review

2021 ◽  
Vol 16 (1) ◽  
Author(s):  
Bogyeong Han ◽  
Juhwan Lee ◽  
Yoon Jin Kwak ◽  
Hyun-Young Kim ◽  
Kwang Hoon Lee ◽  
...  
Keyword(s):  
Intron Retention ◽  
Pathological Examination ◽  
Autosomal Dominant Disorder ◽  
Oncogenic Mutation ◽  
Multiple Organs ◽  
Intronic Mutation ◽  
Abdominal Masses ◽  
Whole Transcriptome Sequencing ◽  
Intron Mutation ◽  
Relationship Of

Abstract Background Tuberous sclerosis complex (TSC) is an autosomal dominant disorder characterized by hamartomas in multiple organs associated with germline mutations in TSC1 and TSC2, including exonic, intronic, or mosaic mutations. Gastrointestinal (GI) tract Lymphangioleiomyomatosis (LAM) is an extremely rare manifestation of TSC, with few reported cases. Herein, we aimed to determine the driver mutation, pathogenesis, and relationship of germline and somatic mutations of LAM through whole-genome sequencing (WGS) of the tumor and blood samples and whole transcriptome sequencing (WTS) analysis. Case presentation A nine-year-old girl with a full-blown TSC presented with abdominal masses detected during a routine check-up. Resected intestinal masses were diagnosed as LAM by thorough pathological examination. Interestingly, the LAM presented a somatic TSC2 gene mutation in exon 24 (p.R905W, c.C2713T), and the patient had intron retention by a novel germline mutation in the intron region of TSC2 (chr16:2126489, C > G). Conclusion Our case suggests that intron retention by a single nucleotide intronic mutation of TSC2 is sufficient to develop severe manifestations of TSC, but the development of LAM requires an additional somatic oncogenic mutation of TSC2.

scholarly journals A Second Hit Somatic (P.R905W) and a Novel Germline Intron-Mutation of TSC2 Gene is Found in Intestinal Lymphangioleiomyomatosis: A Case Report with Literature Review

2021 ◽  
Author(s):  
Bogyeong Han ◽  
Juhwan Lee ◽  
Yoon Jin Kwak ◽  
Hyun-Young Kim ◽  
Kwang Hoon Lee ◽  
...  
Keyword(s):  
Intron Retention ◽  
Pathological Examination ◽  
Autosomal Dominant Disorder ◽  
Oncogenic Mutation ◽  
Intronic Mutation ◽  
Abdominal Masses ◽  
Whole Transcriptome Sequencing ◽  
Intron Region ◽  
Intron Mutation ◽  
Relationship Of

Abstract Background: Tuberous sclerosis complex (TSC) is an autosomal dominant disorder associated with germline mutations in TSC1 and TSC2, including exonic, intronic, or mosaic mutations. Gastrointestinal (GI) tract Lymphangioleiomyomatosis (LAM) is an extremely rare manifestation of TSC, with few reported cases. Herein, we aimed to determine the driver mutation, pathogenesis, and relationship of germline and somatic mutations of LAM through whole-genome sequencing (WGS) of the tumor and blood samples and whole transcriptome sequencing (WTS) analysis. Case presentation: A nine-year-old girl with a full-blown TSC presented with abdominal masses detected during a routine check-up. Resected intestinal masses were diagnosed as LAM by thorough pathological examination. Interestingly, the LAM presented a somatic TSC2 gene mutation in exon 24 (p.R905W, c.C2713T), and the patient had intron retention by a novel germline mutation in the intron region of TSC2 (chr16:2126489, C>G). Conclusion: Our case suggests that intron retention by a single nucleotide intronic mutation of TSC2 is sufficient to develop severe manifestations of TSC, but the development of LAM requires an additional somatic oncogenic mutation.

scholarly journals Giant cystic malignant pheochromocytoma invading right hepatic lobe: report on two cases

2008 ◽  
Vol 126 (4) ◽  
pp. 229-231 ◽  
Author(s):  
Sergio Renato Pais Costa ◽  
Nivaldo Marques Cabral ◽  
Ademir Torres Abhrão ◽  
Ricardo Borges da Costa ◽  
Lilian Mary da Silva ◽  
...  
Keyword(s):  
Abdominal Mass ◽  
Radical Right ◽  
Right Hepatectomy ◽  
Hepatic Tumors ◽  
Hepatic Lobe ◽  
Multiple Organs ◽  
Abdominal Masses ◽  
Retroperitoneal Sarcomas ◽  
The Right ◽  
Radiological Methods

CONTEXT: Cystic pheochromocytomas are uncommon neuroendocrine tumors that originate from the adrenal medulla. Differing from the more frequent solid pheochromocytomas, which produce catecholamines and present adrenergic syndrome, cystic pheochromocytomas may not produce these. Their symptoms are generally associated with an abdominal mass or even pain, particularly if the mass attains large dimensions. Similarly, radiological diagnosis may also be difficult. Right-side lesions may be confounded with cystic hepatic tumors or even retroperitoneal sarcomas with cystic areas, using radiological methods. Sometimes, there may be a preoperative diagnosis of malignancy. Invasion of organs in this region (i.e. liver or kidney), or even the presence of a large retroperitoneal mass (of uncertain origin) with which multiple organs are involved, may be indicative of malignant origin. CASE REPORT: Two cases of giant cystic pheochromocytoma that invaded the right hepatic lobe are described. These presented as abdominal masses. Both cases were malignant. They were treated by radical right nephrectomy plus right hepatectomy.

Intronic SMCHD1 variants in FSHD: testing the potential for CRISPR-Cas9 genome editing

2019 ◽  
Vol 56 (12) ◽  
pp. 828-837 ◽  
Author(s):  
Remko Goossens ◽  
Marlinde L van den Boogaard ◽  
Richard J L F Lemmers ◽  
Judit Balog ◽  
Patrick J van der Vliet ◽  
...  
Keyword(s):  
Genome Editing ◽  
Intron Retention ◽  
Wild Type ◽  
Repeat Array ◽  
D4z4 Repeat ◽  
Intronic Mutation ◽  
Whole Exome ◽  
Efficient Suppression ◽  
The Common ◽  
Chromatin Relaxation

BackgroundFacioscapulohumeral dystrophy (FSHD) is associated with partial chromatin relaxation of the DUX4 retrogene containing D4Z4 macrosatellite repeats on chromosome 4, and transcriptional de-repression of DUX4 in skeletal muscle. The common form of FSHD, FSHD1, is caused by a D4Z4 repeat array contraction. The less common form, FSHD2, is generally caused by heterozygous variants in SMCHD1.MethodsWe employed whole exome sequencing combined with Sanger sequencing to screen uncharacterised FSHD2 patients for extra-exonic SMCHD1 mutations. We also used CRISPR-Cas9 genome editing to repair a pathogenic intronic SMCHD1 variant from patient myoblasts.ResultsWe identified intronic SMCHD1 variants in two FSHD families. In the first family, an intronic variant resulted in partial intron retention and inclusion of the distal 14 nucleotides of intron 13 into the transcript. In the second family, a deep intronic variant in intron 34 resulted in exonisation of 53 nucleotides of intron 34. In both families, the aberrant transcripts are predicted to be non-functional. Deleting the pseudo-exon by CRISPR-Cas9 mediated genome editing in primary and immortalised myoblasts from the index case of the second family restored wild-type SMCHD1 expression to a level that resulted in efficient suppression of DUX4.ConclusionsThe estimated intronic mutation frequency of almost 2% in FSHD2, as exemplified by the two novel intronic SMCHD1 variants identified here, emphasises the importance of screening for intronic variants in SMCHD1. Furthermore, the efficient suppression of DUX4 after restoring SMCHD1 levels by genome editing of the mutant allele provides further guidance for therapeutic strategies.

scholarly journals Von Hippel-Lindau Syndrome- A Case Report

2020 ◽  
Vol 1 (1) ◽  
pp. 25-28
Author(s):  
Suraj Thulung ◽  
Ashish Baniya ◽  
Subodh Sharma Paudel ◽  
Anirudra Devkota ◽  
Shikher Shrestha
Keyword(s):  
Malignant Tumors ◽  
Obstructive Hydrocephalus ◽  
Positive Family History ◽  
Pancreatic Cysts ◽  
Third Ventriculostomy ◽  
Autosomal Dominant Disorder ◽  
Von Hippel Lindau ◽  
Variable Expression ◽  
Multiple Organs ◽  
Gradual Onset

Von Hippel–Lindau (VHL) disease is a rare, familial disorder involving multiple organs, and characterized by the development of many benign and malignant tumors. It is an autosomal dominant disorder with high penetrance and variable expression. We present a case of a 31-year-old gentleman with gradual onset painless bilateral diminution in the vision for one and a half months with significant positive family history. Radiographic study revealed multiple cerebellar hemangioblastomas with obstructive hydrocephalus, renal cortical and pancreatic cysts and cystic renal cell carcinoma. Symptoms were relieved after endoscopic third ventriculostomy. These constellations of findings suggested von Hippel Lindau (VHL) syndrome and we present this case.

The Relationship of Intrauterine Growth Restriction with Placental Pathologic Changes in Newborns

2020 ◽  
Author(s):  
Hossein Dalili ◽  
Fatemeh Sadat Nayeri ◽  
Seyed Reza Mirjalili ◽  
Seyyed Nasrollah Hossein ◽  
Alireza Abdollahi ◽  
...  
Keyword(s):  
Intrauterine Growth Restriction ◽  
Growth Restriction ◽  
Pathological Examination ◽  
Histological Changes ◽  
Intrauterine Growth ◽  
Study Population ◽  
The Mean ◽  
Relationship Of ◽  
The Relationship ◽  
Restriction Group

Introduction: Intrauterine growth restriction is a multifaceted problem and is associated with a significant increase in the level of morbidity and perinatal mortality. According to some studies, failure of the placenta is responsible for the most cases of intrauterine growth restriction. The aim of this study was to evaluate the placental pathologic changes in the intrauterine growth restriction (IUGR) samples and compare them with normal cases.   Methods: A study population consisted of 60 intrauterine growth restriction neonates and 60 normalized neonates born at Tehran Imam Khomeini Hospital between June 2016 and July 2017. The placenta was weighed, immediately after delivery, and the umbilical cord was separated, then stored in 10% formalin and sent for pathological examination as soon as possible. Data collection was performed according to the following items: the pathologist's report, the results of the infants' examination, and the data in the neonatal cases.   Results: The intrauterine growth restriction group showed a high frequency of placenta infarction (P < 0.001), inflammation of the villous (P < 0.001), villous fibrosis (P = 0.044), villous vascularization disorder (P = 0.001), prevalence of chorioamnionitis (P = 0.027), prevalence of Syncytiotrophoblastic knots (P < 0.001) and placental necrosis (P = 0.048) than normal group. However, the mean weight of the placenta (P < 0.001), the length and width of the macroscopic placenta changes was less (P < 0.001).   Conclusion: The results of the current study showed that a major part of the macroscopic and histological changes are detectable in the intrauterine growth restriction samples, which are considerably more common than normal, although they are not pathognomonic, but in the future, more accurate results can be obtained from more extensive studies.

Delayed appearance of carbon granulomas of the scalp after use of carbon fiber pins for refixation of a stereotactic head frame

2001 ◽  
Vol 95 (1) ◽  
pp. 129-131 ◽  
Author(s):  
William E. McCormick ◽  
Gene H. Barnett ◽  
David M. Peereboom ◽  
Glen H. J. Stevens ◽  
Charles V. Biscotti
Keyword(s):  
Carbon Fiber ◽  
Carbon Deposition ◽  
Treatment Strategies ◽  
Content Type ◽  
Head Fixation ◽  
Multiple Organs ◽  
Cutaneous Granuloma ◽  
Relationship Of ◽  
The Relationship ◽  
Fine Print

✓ The authors present a case involving the formation of several carbon granulomas in the scalp of a woman 7 years after she underwent craniotomy. Her operation had included the use of carbon fiber pins for refixation of a stereotactic head frame. Carbon granulomas have been noted in multiple organs following surgical or traumatic carbon deposition, but have not been reported in association with neurosurgical carbon fiber pins used for head fixation. The lesions in this case arose a few months after initiation of chemotherapy for the patient's brain tumor. The relationship of carbon and cutaneous granuloma formation to adjuvant therapies and treatment strategies is discussed.

Similarities and differences in the subcellular localization of hamartin and tuberin in the kidney

2000 ◽  
Vol 278 (5) ◽  
pp. F737-F746 ◽  
Author(s):  
Vanishree Murthy ◽  
Luciana A. Haddad ◽  
Nicole Smith ◽  
Denise Pinney ◽  
Robert Tyszkowski ◽  
...  
Keyword(s):  
Apical Membrane ◽  
Cell Types ◽  
Intercalated Cells ◽  
Autosomal Dominant Disorder ◽  
Specific Expression ◽  
Multiple Organs ◽  
Distal Tubules ◽  
Kidney Lesions ◽  
The Brain

Tuberous sclerosis complex (TSC) is an autosomal dominant disorder characterized by hamartomas in multiple organs, notably the brain and kidneys. The disease is caused by mutations in TSC1or TSC2 genes, coding hamartin and tuberin, respectively. Immunofluorescence analysis of tuberin and hamartin performed here demonstrates that both proteins are specifically expressed in the distal urinary tubule, comprising the distal tubules, connecting segment, and collecting ducts. Hamartin, distinct from tuberin, is expressed in the thick ascending limbs of Henle and in juxtaglomerular cells, where it colocalizes with renin. In positive epithelial cells, tuberin localizes to the cytoplasm as well as the apical membrane. Hamartin, however, preferentially localizes to the apical membrane. The two proteins colocalize at the apical membrane of type A intercalated cells and connecting tubule cells, whereas in type B intercalated cells they reveal a variable pattern of expression. The cell-specific expression of tuberin and hamartin described here will provide critical insight into the cell types that give rise to kidney lesions, and the tumor suppressor role of these proteins in TSC.

scholarly journals A deep intronic mutation in AR gene causing androgen insensitivity syndrome: difficulties of diagnostics

2021 ◽  
Vol 67 (5) ◽  
pp. 48-52
Author(s):  
N. Y. Kalinchenko ◽  
V. M. Petrov ◽  
A. V. Panova ◽  
A. N. Tiulpakov
Keyword(s):  
Genetic Diagnosis ◽  
Androgen Insensitivity Syndrome ◽  
Splice Acceptor Site ◽  
Acceptor Site ◽  
Coding Region ◽  
Sex Development ◽  
Intronic Mutation ◽  
Androgen Resistance ◽  
Differences Of Sex Development ◽  
Intron Mutation

Partial androgen resistance syndrome (PAIS) is the most difficult form of disorders/differences of sex development 46,XY (DSD 46,XY) for choosing of patient management. To date, there are no clear biochemical criteria, especially before puberty, that allow differentiating PAIS from other PAIS-like forms of DSD 46, XY, and genetic verification of the partial form of AIS plays an important role. Meanwhile, according to the literature, mutations in the coding region of AR gene have not been identified in more than 50% of patients with suspected AIS. We performed an extensive analysis of the AR gene in a patient with clinical and laboratory signs of AIS and found a deep intron mutation in the AR gene (p. 2450–42G>A). This variant creates an alternative splice acceptor site resulted a disturbance of the AR function. These findings indicate the need for extensive genetic analysis in a cohort of patients with suspected CPA in the absence of mutations in the AR gene using standard methods of genetic diagnosis.

scholarly journals An Update on the Relationship of SARS-CoV-2 and Male Reproduction

2021 ◽  
Vol 12 ◽  
Author(s):  
Juncen Guo ◽  
Kai Sheng ◽  
Sixian Wu ◽  
Hanxiao Chen ◽  
Wenming Xu
Keyword(s):  
Male Reproduction ◽  
Panoramic View ◽  
Viral Receptor ◽  
Angiotensin Converting Enzyme 2 ◽  
Multiple Organs ◽  
The World ◽  
New Perspective ◽  
Relationship Of ◽  
The Impact ◽  
The Relationship

Since the outbreak of the COVID-19, up to now, infection cases have been continuously rising to over 200 million around the world. Male bias in morbidity and mortality has emerged in the COVID-19 pandemic. The infection of SARS-CoV-2 has been reported to cause the impairment of multiple organs that highly express the viral receptor angiotensin-converting enzyme 2 (ACE2), including lung, kidney, and testis. Adverse effects on the male reproductive system, such as infertility and sexual dysfunction, have been associated with COVID-19. This causes a rising concern among couples intending to have a conception or who need assisted reproduction. To date, a body of studies explored the impact of SARS-CoV-2 on male reproduction from different aspects. This review aims to provide a panoramic view to understand the effect of the virus on male reproduction and a new perspective of further research for reproductive clinicians and scientists.

scholarly journals A 28-Year-Old Male Patient with Nail Tumors, Skin Lesions, and Epilepsy

2017 ◽  
Vol 9 (1) ◽  
pp. 12-19
Author(s):  
Deepak M.W. Balak ◽  
Bernard A. Zonnenberg ◽  
Juliette M.J.  Spitzer-Naaijkens ◽  
Mieke M. Hulshof
Keyword(s):  
Differential Diagnosis ◽  
Older Patients ◽  
Autosomal Dominant ◽  
Skin Lesions ◽  
Histopathological Analysis ◽  
Autosomal Dominant Disorder ◽  
Cutaneous Manifestations ◽  
Multiple Organs ◽  
Lower Back ◽  
Giant Cell Astrocytoma

Background: Tuberous sclerosis complex (TSC) is an autosomal dominant disorder characterized by the development of benign hamartomas in multiple organs. Most patients with TSC exhibit cutaneous manifestations. Methods: We report a 28-year-old patient with multiple pink papules at the proximal nail fold of several toes. Results: Histopathological analysis of a biopsy of a papule was consistent with an ungual fibroma. Histopathological analysis of a biopsy of an elevated skin-colored plaque at the lower back was diagnostic for a Shagreen patch. These findings were consistent with a clinical diagnosis of TSC. This patient was subsequently referred to a multidisciplinary TSC clinic for further screening, which revealed a giant cell astrocytoma and multiple subependymal tubers. Annual monitoring was recommended. The skin lesions were treated with topical rapamycin ointment. Conclusions: Recognizing dermatological manifestations of TSC is of importance to allow early diagnosis. TSC should be considered as a differential diagnosis in the case of ungual fibromas, even in older patients.

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