scholarly journals De Novo PTEN Mutation in a Young Boy with Cutaneous Vasculitis

2017 ◽  
Vol 2017 ◽  
pp. 1-4 ◽  
Author(s):  
Angela Mauro ◽  
Ebun Omoyinmi ◽  
Neil James Sebire ◽  
Angela Barnicoat ◽  
Paul Brogan
Keyword(s):  
De Novo ◽  
Cowden Syndrome ◽  
Cancer Surveillance ◽  
Cutaneous Vasculitis ◽  
De Novo Mutation ◽  
Proteus Syndrome ◽  
Targeted Next Generation Sequencing ◽  
Tensin Homolog ◽  
Increased Risk ◽  
Risk Of Malignancy

Phosphatase and tensin homolog (PTEN) is the protein encoded by the PTEN gene (10q23.3). PTEN mutations are related to a variety of rare diseases referred to collectively as PTEN hamartoma tumor syndromes (PHTS), which include Cowden Syndrome, Bannayan-Riley-Ruvalcaba syndrome, Proteus Syndrome, and Proteus-like syndrome. These diseases are associated with an increased risk of malignancy and for this reason an accurate and early diagnosis is essential in order to institute cancer surveillance. PTEN is a regulator of growth and homeostasis in immune system cells, although there are limited data describing immune dysregulation caused by PTEN mutations. We describe a case of PHTS syndrome caused by a de novo mutation in PTEN detected using a targeted next generation sequencing (NGS) gene panel which was instigated for workup of cutaneous vasculitis. We highlight the diagnostic utility of this approach and that mutations in PTEN may be associated with immune-dysregulatory features such as vasculitis in young children.

Targeted Resequencing of Putative Growth-Related Genes Using Whole Exome Sequencing in Patients with Severe Primary IGF-I Deficiency

2017 ◽  
Vol 88 (6) ◽  
pp. 408-417 ◽  
Author(s):  
Greta Grosse ◽  
Alina Hilger ◽  
Michael Ludwig ◽  
Heiko Reutter ◽  
Franziska Lorenzen ◽  
...  
Keyword(s):  
Large Scale ◽  
De Novo ◽  
Targeted Resequencing ◽  
Targeted Next Generation Sequencing ◽  
Increased Risk ◽  
Igf I ◽  
Novel Variant ◽  
Unaffected Parent ◽  
Next Generation Sequencing Ngs ◽  
Clinical Phenotyping

Background/Aims: To elucidate the genetic causes of severe primary insulin-like growth factor-I deficiency (SPIGFD) by systematic, targeted, next-generation sequencing (NGS)-based resequencing of growth-related genes. Methods: Clinical phenotyping followed by NGS in 17 families including 6 affected sib pairs. Results: We identified disease-causing, heterozygous, de novo variants in HRAS (p.Gly13Cys) and FAM111A (p.Arg569His) in 2 male patients with syndromic SPIGFD. A previously described homozygous GHR nonsense variant was detected in 2 siblings of a consanguineous family (p.Glu198*). Furthermore, we identified an inherited novel variant in the IGF2 gene (p.Arg156Cys) of a maternally imprinted gene in a less severely affected father and his affected daughter. We detected 2 other novel missense variants in SH2B1 and SOCS2, both were inherited from an unaffected parent. Conclusions: Screening of growth-related genes using NGS-based, large-scale, targeted resequencing identified disease-causing variants in HRAS, FAM111A, and GHR. Considering the increased risk of subjects with HRAS mutations for neoplasms, close clinical monitoring and a thorough discussion of the risk/benefit ratio of the treatment with recombinant IGF-I is mandatory. Segregation analysis proved to be critical in the interpretation of potential SPIGFD-associated gene variations.

scholarly journals Cowden Syndrome: report of a case and brief review of literature

2013 ◽  
Vol 88 (6 suppl 1) ◽  
pp. 52-52 ◽  
Author(s):  
Ana Carolina Souza Porto ◽  
Elisabeth Roider ◽  
Thomas Ruzicka
Keyword(s):  
Cell Cycle Progression ◽  
Cowden Syndrome ◽  
Pten Gene ◽  
Benign Tumors ◽  
Cutaneous Lesions ◽  
Phosphatase And Tensin Homolog ◽  
Tensin Homolog ◽  
Increased Risk ◽  
History Of ◽  
Risk Of Cancer

We present the case of a female patient with facial cutaneous lesions, a cobblestone-like pattern of the oral mucosa, and verruciform lesions on the hand since her youth. She reported a history of breast cancer, endometrial cancer, melanoma and multiple benign tumors and cysts. PTEN gene analysis was performed and confirmed Cowden Syndrome, a rare genodermatosis with an autosomal dominant pattern of inheritance, characterized by multiple hamartomas. The phosphatase and tensin homolog (PTEN) gene negatively regulates cell proliferation and cell cycle progression. Loss of PTEN function contributes to an increased risk of cancer. We emphasize the importance of early detection and accurate management of Cowden Syndrome.

scholarly journals Schinzel-Giedion Syndrome with Congenital Megacalycosis in a Turkish Patient: Report of SETBP1 Mutation and Literature Review of the Clinical Features

2017 ◽  
Vol 2017 ◽  
pp. 1-4
Author(s):  
Ozgul Bulut ◽  
Zeynep Ince ◽  
Umut Altunoglu ◽  
Sukran Yildirim ◽  
Asuman Coban
Keyword(s):  
Literature Review ◽  
Autosomal Dominant ◽  
De Novo ◽  
Facial Dysmorphism ◽  
Multiple Congenital Anomalies ◽  
Patient Report ◽  
Autosomal Dominant Disorder ◽  
Turkish Patient ◽  
Increased Risk ◽  
Risk Of Malignancy

Schinzel-Giedion syndrome (SGS) is a rare autosomal dominant disorder that results in facial dysmorphism, multiple congenital anomalies, and an increased risk of malignancy. Recently, using exome sequencing, de novo heterozygous mutations in the SETBP1 gene have been identified in patients with SGS. Most affected individuals do not survive after childhood because of the severity of this disorder. Here, we report SETBP1 mutation confirmed by molecular analysis in a case of SGS with congenital megacalycosis.

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.

scholarly journals Pediatric leukemia susceptibility disorders: manifestations and management

Hematology ◽  
2017 ◽  
Vol 2017 (1) ◽  
pp. 242-250 ◽  
Author(s):  
Lisa J. McReynolds ◽  
Sharon A. Savage
Keyword(s):  
Early Onset ◽  
Ribosome Biogenesis ◽  
De Novo ◽  
Disease Risk ◽  
Bone Marrow Failure ◽  
Clinical Manifestations ◽  
Cancer Surveillance ◽  
Therapeutic Interventions ◽  
Pediatric Leukemia ◽  
Inherited Susceptibility

Abstract The clinical manifestations of inherited susceptibility to leukemia encompass a wide phenotypic range, including patients with certain congenital anomalies or early-onset myelodysplastic syndrome (MDS) and some with no obvious medical problems until they develop leukemia. Leukemia susceptibility syndromes occur as a result of autosomal dominant, autosomal recessive, or X-linked recessive inheritance, or de novo occurrence, of germline pathogenic variants in DNA repair, ribosome biogenesis, telomere biology, hematopoietic transcription factors, tumor suppressors, and other critical cellular processes. Children and adults with cytopenias, MDS, dysmorphic features, notable infectious histories, immunodeficiency, certain dermatologic findings, lymphedema, unusual sensitivity to radiation or chemotherapy, or acute leukemia with a family history of early-onset cancer, pulmonary fibrosis, or alveolar proteinosis should be thoroughly evaluated for a leukemia susceptibility syndrome. Genetic testing and other diagnostic modalities have improved our ability to identify these patients and to counsel them and their family members for subsequent disease risk, cancer surveillance, and therapeutic interventions. Herein, the leukemia susceptibility syndromes are divided into 3 groups: (1) those associated with an underlying inherited bone marrow failure syndrome, (2) disorders in which MDS precedes leukemia development, and (3) those with a risk primarily of leukemia. Although children are the focus of this review, it is important for clinicians to recognize that inherited susceptibility to cancer can present at any age, even in older adults; genetic counseling is essential and prompt referral to experts in each syndrome is strongly recommended.

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