scholarly journals Expanding the Clinical Spectrum of Sotos Syndrome in a Patient with the New “c.[5867T>A]+[=]”; “p.[Leu1956Gln]+[=]” NSD1 Missense Mutation and Complex Skin Hamartoma

2018 ◽  
Vol 19 (10) ◽  
pp. 3189
Author(s):  
Annalisa Mencarelli ◽  
Paolo Prontera ◽  
Amedea Mencarelli ◽  
Daniela Rogaia ◽  
Gabriela Stangoni ◽  
...  
Keyword(s):  
Missense Mutation ◽  
Clinical Features ◽  
De Novo ◽  
Genetic Disorder ◽  
Control Cell ◽  
Functional Domain ◽  
Sotos Syndrome ◽  
Organ Systems ◽  
Increased Risk ◽  
The Right

Sotos syndrome is one of the most common overgrowth diseases and it predisposes patients to cancer, generally in childhood. The prevalence of this genetic disorder is 1:10,000–1:50,000, and it is characterized by wide allelic heterogeneity, with more than 100 different known mutations in the nuclear receptor-binding SET domain containing protein 1 (NSD1) gene. Most of these alterations are deletions and common micro-deletions with haploinsufficiency. Singular variants are missense mutations. The present study reports a case of a 4-year-old boy with specific clinical features of Sotos syndrome and a particular complex skin hamartoma on the right femoral side, in addition to other minor findings, such as a “café-au-lait” spot on the right hemithorax and syndactyly of the second and third right toes. NSD1 gene analysis identified a de novo missense mutation, “c.[5867T>A]+[=]”; “p.[Leu1956Gln]+[=]”, that was not previously described in the literature. This mutation was localized to the functional domain of the gene and was likely the cause of Sotos syndrome in our patient. We also compared aspects of our patient’s condition with the clinical features of tuberous sclerosis (TSC), which is an autosomal neurocutaneous syndrome caused by mutations in the TSC1/TSC2 genes. These genes control cell growth and cell survival. This disorder is characterized by hamartomas in multiple organ systems, several coetaneous abnormalities, epilepsy, and increased risk of several types of tumors.

scholarly journals A New Case of 13q12.2q13.1 Microdeletion Syndrome Contributes to Phenotype Delineation

2014 ◽  
Vol 2014 ◽  
pp. 1-5
Author(s):  
Giorgia Mandrile ◽  
Eleonora Di Gregorio ◽  
Alessandro Calcia ◽  
Alessandro Brussino ◽  
Enrico Grosso ◽  
...  
Keyword(s):  
Clinical Features ◽  
Critical Region ◽  
Array Cgh ◽  
De Novo ◽  
Genetic Disorder ◽  
Phenotypic Expression ◽  
Microdeletion Syndrome ◽  
Complex Rearrangement

A recently described genetic disorder has been associated with 13q12.3 microdeletion spanning three genes, namely,KATNAL1, LINC00426, andHMGB1. Here, we report a new case with similar clinical features that we have followed from birth to 5 years old. The child carried a complex rearrangement with a double translocation: 46,XX,t(7;13)(p15;q14),t(11;15)(q23;q22). Array-CGH identified ade novomicrodeletion at 13q12.2q13.1 spanning 3–3.4 Mb and overlapping 13q12.3 critical region. Clinical features resembling those reported in the literature confirm the existence of a distinct 13q12.3 microdeletion syndrome and provide further evidence that is useful to characterize its phenotypic expression during the 5 years of development.

Composites and Structures for Regenerative Engineering

2014 ◽  
Vol 1621 ◽  
pp. 3-15 ◽  
Author(s):  
Cato T. Laurencin ◽  
Roshan James
Keyword(s):  
Cell Fate ◽  
Soft Tissues ◽  
De Novo ◽  
Control Cell ◽  
Continuous Phase ◽  
Lessons Learned ◽  
Regenerative Capacity ◽  
Regenerative Engineering ◽  
Organ Systems ◽  
Increasing Demand

ABSTRACTRegenerative engineering was conceptualized by bridging the lessons learned in developmental biology and stem cell science with biomaterial constructs and engineering principles to ultimately generate de novo tissue. We seek to incorporate our understanding of natural tissue development to design tissue-inducing biomaterials, structures and composites than can stimulate the regeneration of complex tissues, organs, and organ systems through location-specific topographies and physico-chemical cues incorporated into a continuous phase. This combination of classical top-down tissue engineering approach with bottom-up strategies used in regenerative biology represents a new multidisciplinary paradigm. Advanced surface topographies and material scales are used to control cell fate and the consequent regenerative capacity.Musculoskeletal tissues are critical to the normal functioning of an individual and following damage or degeneration they show extremely limited endogenous regenerative capacity. The increasing demand for biologically compatible donor tissue and organ transplants far outstrips the availability leading to an acute shortage. We have developed several biomimetic structures using various biomaterial platforms to combine optimal mechanical properties, porosity, bioactivity, and functionality to effect repair and regeneration of hard tissues such as bone, and soft tissues such as ligament and tendon. Starting with simple structures, we have developed composite and multi-scale systems that very closely mimic the native tissue architecture and material composition. Ultimately, we aim to modulate the regenerative potential, including proliferation, phenotype maturation, matrix production, and apoptosis through cell-scaffold and host –scaffold interactions developing complex tissues and organ systems.

scholarly journals Prader-Willi Syndrome due to an Unbalanced de novo Translocation t(15;19)(q12;p13.3)

2016 ◽  
Vol 150 (1) ◽  
pp. 29-34 ◽  
Author(s):  
Vy Dang ◽  
Abhilasha Surampalli ◽  
Ann M. Manzardo ◽  
Stephanie Youn ◽  
Merlin G. Butler ◽  
...  
Keyword(s):  
De Novo ◽  
Chromosome Region ◽  
Genetic Disorder ◽  
Type I ◽  
Prader Willi Syndrome ◽  
Stk11 Gene ◽  
Feeding Difficulties ◽  
First Case ◽  
Increased Risk ◽  
Hands And Feet

Prader-Willi syndrome (PWS) is a complex, multisystem genetic disorder characterized by endocrine, neurologic, and behavioral abnormalities. We report the first case of an unbalanced de novo reciprocal translocation of chromosomes 15 and 19, 45,XY,-15,der(19)t(15;19)(q12;p13.3), resulting in monosomy for the PWS critical chromosome region. Our patient had several typical features of PWS including infantile hypotonia, a poor suck and feeding difficulties, tantrums, skin picking, compulsions, small hands and feet, and food seeking, but not hypopigmentation, a micropenis, cryptorchidism or obesity as common findings seen in PWS at the time of examination at 6 years of age. He had seizures noted from 1 to 3 years of age and marked cognitive delay. High-resolution SNP microarray analysis identified an atypical PWS type I deletion in chromosome 15 involving the proximal breakpoint BP1. The deletion extended beyond the GABRB3 gene but was proximal to the usual distal breakpoint (BP3) within the 15q11q13 region, and GABRA5, GABRG3, and OCA2 genes were intact. No deletion of band 19p13.3 was detected; therefore, the patient was not at an increased risk of tumors from the Peutz-Jeghers syndrome associated with a deletion of the STK11 gene.

scholarly journals Novel TNC-PDGFD fusion in fibrosarcomatous dermatofibrosarcoma protuberans: a case report

2021 ◽  
Vol 16 (1) ◽  
Author(s):  
Yuan Chen ◽  
Ying-zhou Shi ◽  
Xiao-he Feng ◽  
Xiao-tong Wang ◽  
Xiang-lei He ◽  
...  
Keyword(s):  
De Novo ◽  
Polymerase Chain Reaction Amplification ◽  
Smooth Muscle Actin ◽  
Dermatofibrosarcoma Protuberans ◽  
Fusion Transcript ◽  
Metastatic Potential ◽  
Chromosome Translocation ◽  
High Rate ◽  
Increased Risk ◽  
The Right

Abstract Background Dermatofibrosarcoma protuberans (DFSP) is a superficial fibroblastic tumor characterized by high rate of local recurrence and low metastatic potential. Fibrosarcomatous transformation can rarely arise in DFSP either de novo or as recurrent, which represents a form of tumor progression and carries an increased risk of metastasis over classic DFSP. Cytogenetically, DFSP is characterized by a recurrent unbalanced chromosome translocation t (17;22)(q22;q13), leading to the formation of COL1A1-PDGFB fusion transcript that is present in more than 90% of cases. Alternative fusions involving the PDGFD with partners of COL6A3 or EMILIN2 have recently been documented in less than 2% of cases. Herein, we report a DFSP with fibrosarcomtous morphology harboring a novel TNC-PDGFD fusion. Case presentation A 54-year-old female presented with a slowly growing mass in the right thigh. Excision demonstrated a 2-cm ovoid, well-circumscribed, gray-white, mass. Microscopic examination revealed a partially encapsulated subcutaneous nodule without dermal connection. The neoplasm was composed of cellular and fairly uniform spindle cells with brisk mitoses, arranged in elongated fascicles and herringbone patterns, with focal collagenized stroma. The neoplastic cells were positive for CD34 and smooth muscle actin. Fluorescence in-situ hybridization analyses showed negative for COL1A1-PDGFB fusion as well as NTRK1/2/3 rearrangements. A subsequent RNA sequencing detected an in-frame fusion between exon 15 of TNC and exon 6 of PDGFD. This fusion was further confirmed by nested reverse transcription polymerase chain reaction amplification followed by Sanger sequencing. A diagnosis of fibrosarcomatous DFSP was rendered and the patient was in good status at a follow-up of 12 months after the operation. Conclusions We report a fibrosarcomatous DFSP with novel TNC-PDGFD fusion, which adds to the pathologic and genetic spectrum of PDGFD-rearranged DFSP.

scholarly journals Fraternal twins with Phelan-McDermid syndrome not involving the SHANK3 gene: case report and literature review

2020 ◽  
Vol 13 (1) ◽  
Author(s):  
Shan Li ◽  
Ke-wang Xi ◽  
Ting Liu ◽  
Ying Zhang ◽  
Meng Zhang ◽  
...  
Keyword(s):  
Clinical Features ◽  
De Novo ◽  
Genetic Disorder ◽  
Deletion Syndrome ◽  
Facial Dysmorphism ◽  
Germline Mosaicism ◽  
Third Generation Sequencing ◽  
Neurological Features ◽  
Hands And Feet ◽  
Abnormal Behaviors

Abstract Background Phelan-McDermid syndrome (PMS, OMIM#606232), or 22q13 deletion syndrome, is a rare genetic disorder caused by deletion of the distal long arm of chromosome 22 with a variety of clinical features that display considerably heterogeneous degrees of severity. The SHANK3 gene is understood to be the critical gene for the neurological features of this syndrome. Case presentation We describe one pair of boy-girl twins with a 22q13 deletion not involving the SHANK3 gene. Interestingly, the clinical and molecular findings of the two patients were identical, likely resulting from germline mosaicism in a parent. The boy-girl twins showed intellectual disability, speech absence, facial dysmorphism, cyanosis, large fleshy hands and feet, dysplastic fingernails and abnormal behaviors, and third-generation sequencing showed an identical de novo interstitial deletion of 6.0 Mb in the 22q13.31-q13.33 region. Conclusions Our case suggests that prenatal diagnosis is essential for normal parents with affected children due to the theoretical possibility of parental germline mosaicism. Our results also indicated that other genes located in the 22q13 region may have a role in explaining symptoms in individuals with PMS. In particular, we propose that four candidate genes, CELSR1, ATXN10, FBLN1 and WNT7B, may also be involved in the etiology of the clinical features of PMS. However, more studies of smaller interstitial deletions with 22q13 are needed to corroborate our hypothesis and better define the genotype-phenotype correlation. Our findings contribute to a more comprehensive understanding of PMS.

Aortic Thrombus Embolization in A Patient with Tuberous Sclerosis

2021 ◽  
Author(s):  
Steven Wolf ◽  
Andrew Rhoads ◽  
William Gomes ◽  
Philip Overby ◽  
Patricia McGoldrick
Keyword(s):  
Cerebral Infarction ◽  
Tuberous Sclerosis ◽  
Genetic Disorder ◽  
Altered Mental Status ◽  
Unknown Etiology ◽  
Benign Tumors ◽  
Organ Systems ◽  
Aortic Thrombus ◽  
History Of ◽  
The Right

AbstractTuberous sclerosis complex (TSC) is an autosomal dominant genetic disorder affecting many organ systems. Patients commonly develop a variety of benign tumors as well as neurological disease, including seizures, autism, and cognitive delay. We report here the case of an adolescent patient with TSC and a history of mild COVID-19 who presented with a 1-day history of altered mental status. The patient was found to have ischemic cerebral infarction of the right MCA and ACA territories. Initial angiography showed an occlusion of the right internal carotid artery without a demonstrable etiology, with follow-up echocardiography and angiography revealing a large aortic thrombus. The patient was not a candidate for thrombus removal due to her cerebral infarct and received medical anticoagulation. Thrombosis progressed to involve the left ICA, with left cerebral infarction and subsequent death. Aortic thrombus embolization as a cause of cerebrovascular accident (CVA) is a novel finding in the setting of TSC and should be considered for pediatric patients with CVA of unknown etiology. It is unclear whether this was related to the prior COVID-19 infection.

scholarly journals Characterization of Two Loss-of-Function NF1 Variants in Chinese Patients and Potential Molecular Interpretations of Phenotypes

2021 ◽  
Vol 12 ◽  
Author(s):  
Tingting Zhang ◽  
Tianting Han ◽  
Zhiya Dong ◽  
Chuanyin Li ◽  
Wenli Lu
Keyword(s):  
De Novo ◽  
Malignant Tumors ◽  
Genetic Disorder ◽  
Neurofibromatosis Type ◽  
Chinese Patients ◽  
Bone Lesions ◽  
Loss Of Function ◽  
Molecular Sequence ◽  
Increased Risk ◽  
Uncertain Significance

Neurofibromatosis type 1 (NF1) is a common genetic disorder characterized by cafe’-au-lait spots, skinfold freckles, the formation of neurofibromas, skeletal dysplasia, vascular dysplasia, and an increased risk of malignant tumors. In this study, two Chinese NF1 children troubled with bone lesions or hypertension were reported. A de novo NF1 mutation (c.4925T > A/p.V1642E) and a maternally inherited NF1 mutation (c.4883T > A/p.L1628∗) were identified by molecular sequence. According to the ACMG/AMP guidelines, the c.4925T > A was classified as variants of uncertain significance (VOUS) while the c.4883T > A mutation was identified as likely Pathogenic. Further study found that these two NF1 mutants had lost their function to inhibit the Ras/Erk signaling and the proliferation of cells, which could interpretate some phenotypes of these two NF1 patients. We also observed these two NF1 mutants displayed decreased protein stability with increased ubiquitination levels compared with that of wild-type NF1.

scholarly journals Gitelman syndrome caused by a novel hemiallelic missense mutation in SLC12A3 revealed by 16q12.2q21 microdeletion

2020 ◽  
Vol 7 (1) ◽  
Author(s):  
Yuki Abe ◽  
Toshiyuki Yamamoto ◽  
Yukie Izumita ◽  
Shinya Tsukano
Keyword(s):  
Missense Mutation ◽  
Clinical Features ◽  
Autosomal Recessive ◽  
De Novo ◽  
Missense Variant ◽  
Gitelman Syndrome ◽  
Recessive Trait ◽  
Autosomal Recessive Trait ◽  
Biallelic Mutations

AbstractGitelman syndrome (GS) is caused by biallelic mutations in SLC12A3 as an autosomal recessive trait. A patient with a de novo 16q12.2q21 microdeletion showed clinical features of GS. SLC12A3 included in the deletion was analyzed, and a rare missense variant (c.1222A>C [p.N406H]) was identified as hemizygous. Consequently, GS was caused by the revealed SLC12A3 variant owing to chromosomal microdeletion.

scholarly journals Campomelic dysplasia: an overview of a rare genetic disorder

2019 ◽  
Vol 18 (3) ◽  
pp. 67-70
Author(s):  
N. Antonakopoulos ◽  
D. Vrachnis ◽  
N. Loukas ◽  
Ch. Christodoulaki ◽  
Z. Iliodromiti ◽  
...  
Keyword(s):  
De Novo ◽  
Pregnancy Termination ◽  
Genetic Disorder ◽  
Molecular Genetic ◽  
Ambiguous Genitalia ◽  
De Novo Mutation ◽  
Campomelic Dysplasia ◽  
Rare Genetic Disorder ◽  
Radiologic Evaluation ◽  
Increased Risk

Campomelic dysplasia is a rare and severe genetic condition that is characterized by shortening and bowing of the long bones, abnormal face, multiple congenital anomalies, and ambiguous genitalia. Having conducted a review of the existing literature on this rare genetic disorder, we herein present the most pertinent and essential data on the condition viewed from the clinical perspective. In the majority of cases when the neonate survives the condition, since the underlying cause is more often than not a de novo mutation of the SOX9 gene, there is no increased risk of recurrence. Diagnosis is tentatively made based on skeletal findings during routine prenatal ultrasound; it may subsequently be confirmed via either prenatal or postnatal molecular genetic testing or else radiologic evaluation. In general, the condition is considered to be lethal in the neonatal period, there is no prenatal treatment and pregnancy termination is an option.

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