A Patient with Noonan Syndrome with a < b > < i > KRAS < /i > < /b > Mutation Who Presented Severe Nerve Root Hypertrophy
We report a 45-year-old female with clinical features resembling Noonan syndrome (NS) who presented with significant nerve root hypertrophy. She was initially diagnosed with Charcot-Marie-Tooth disease because her gait disturbance gradually deteriorated and nerve conduction velocity was reduced. However, she did not carry aPMP22 gene mutation. RASopathies are a group of phenotypically overlapping developmental syndromes caused by germline mutations that encode components of the Ras/MAPK signaling pathway. These disorders include NS, cardiofaciocutaneous (CFC) syndrome, and Costello syndrome and are associated with molecula...
Source: Case Reports in Neurology - February 16, 2021 Category: Neurology Source Type: research
Musculo-skeletal phenotype of Costello syndrome and cardio-facio-cutaneous syndrome: insights on the functional assessment status
Costello syndrome (CS) and cardio-facio-cutaneous syndrome (CFCS) belong to the RASopathies, a group of neurodevelopmental disorders with skeletal anomalies. Due to their rarity, the characterization of the m... (Source: Orphanet Journal of Rare Diseases)
Source: Orphanet Journal of Rare Diseases - January 22, 2021 Category: Internal Medicine Authors: Chiara Leoni, Domenico Marco Romeo, Michele Pelliccioni, Mariangela Di Gi à, Roberta Onesimo, Valentina Giorgio, Elisabetta Flex, Marta Tedesco, Marco Tartaglia, Donato Rigante, Antonio Valassina and Giuseppe Zampino Tags: Research Source Type: research
Development of Noonan syndrome by deregulation of allosteric SOS autoactivation [Cell Biology]
Ras family proteins play an essential role in several cellular functions, including growth, differentiation, and survival. The mechanism of action of Ras mutants in Costello syndrome and cancers has been identified, but the contribution of Ras mutants to Noonan syndrome, a genetic disorder that prevents normal development in various parts of the body, is unknown. Son of Sevenless (SOS) is a Ras guanine nucleotide exchange factor. In response to Ras-activating cell signaling, SOS autoinhibition is released and is followed by accelerative allosteric feedback autoactivation. Here, using mutagenesis-based kinetic and pulldown ...
Source: Journal of Biological Chemistry - September 24, 2020 Category: Chemistry Authors: Hope Gloria Umutesi, Hanh My Hoang, Hope Elizabeth Johnson, Kwangho Nam, Jongyun Heo Tags: Enzymology Source Type: research
Hyperinsulinemic Hypoglycemia in a Patient with Costello Syndrome: An Etiology to Consider in Hypoglycemia
In this report, we describe a patient with CS accompanied by a clinical picture of hyperinsulinemic hypoglycemia responsive to diazoxide treatment. A 41-day-old female patient with a birth weight of 3,600 g was referred for atypical facial features and swallowing dysfunction. She had a weight of 4,000 g ( −0.8 SDS), a length of 50 cm (−2.4 SDS), and a head circumference of 38 cm (0.2 SDS). The clinical findings were suggestive of a genetic syndrome, mainly a RASopathy or Beckwith-Wiedemann syndrome. Whole exome sequencing revealed a de novo heterozygous missense variant in theHRAS (NM_001130442) gene in exon 2: c.35G#x...
Source: Molecular Syndromology - September 16, 2020 Category: Molecular Biology Source Type: research
RASopathies
are a group of disorders characterized by mutations in the RAS-MAPK pathway. RAS-MAP signaling plays a critical role in cell differentiation, proliferation, and survival. Germline mutations can result in distinctive syndromes, including Noonan syndrome, Costello syndrome, and neurofibromatosis type 1. Mosaic RASopathies can present as localized cutaneous lesions like epidermal nevi and nevus sebaceous, or more extensive conditions such as encephalocraniocutaneous lipomatosis. We review the heterogenous presentation of RAS mutations, discuss new targeted therapies, and highlight areas of uncertainty, including carcinogenes...
Source: Clinics in Dermatology - June 30, 2020 Category: Dermatology Authors: Mustufa Jafry, Robert Sidbury Source Type: research
[Noonan syndrome: genetic and clinical update and treatment options].
Abstract
Noonan syndrome (NS) is a relatively common genetic condition characterised by short stature, congenital heart defects, and distinctive facial features. NS and other clinically overlapping conditions such as NS with multiple lentigines (formerly called LEOPARD syndrome), cardiofaciocutaneous syndrome, or Costello syndrome, are caused by mutations in genes encoding proteins of the RAS-MAPKinases pathway. Because of this shared mechanism, these conditions have been collectively termed «RASopathies». Despite the recent advances in molecular genetics, nearly 20% of patients still lack a genetic caus...
Source: Anales de Pediatria - May 30, 2020 Category: Pediatrics Authors: Carcavilla A, Suárez-Ortega L, Rodríguez Sánchez A, Gonzalez-Casado I, Ramón-Krauel M, Labarta JI, Quinteiro Gonzalez S, Riaño Galán I, López-Siguero JP Tags: An Pediatr (Barc) Source Type: research
miRNA Genetic Variants Alter Their Secondary Structure and Expression in Patients With RASopathies Syndromes
RASopathies are a group of rare genetic diseases caused by germline mutations in genes involved in the RAS–mitogen-activated protein kinase (RAS-MAPK) pathway. Whole-exome sequencing (WES) is a powerful approach for identifying new variants in coding and noncoding DNA sequences, including miRNAs. miRNAs are fine-tuning negative regulators of gene expression. The presence of variants in miRNAs could lead to malfunctions of regulation, resulting in diseases. Here, we identified 41 variants in mature miRNAs through WES analysis in five patients with previous clinical diagnosis of RASopathies syndromes. The pathways, biologi...
Source: Frontiers in Genetics - November 12, 2019 Category: Genetics & Stem Cells Source Type: research
Precocious puberty and Chiari I malformation with syrinx: a case report of an unusual presentation of Costello syndrome
We present a patient with CS and central precocious puberty (CPP). (Source: International Journal of Pediatric Endocrinology)
Source: International Journal of Pediatric Endocrinology - October 22, 2019 Category: Endocrinology Authors: Naomi S. Schwartz and Molly O. Regelmann Tags: Case report Source Type: research
Antenatal diagnosis of cardio-facio-cutaneous syndrome: prenatal characteristics and contribution of fetal facial dysmorphic signs in utero. About a case and review of literature
Publication date: Available online 16 July 2019Source: European Journal of Obstetrics & Gynecology and Reproductive BiologyAuthor(s): Jean-Marc Biard, Patricia Steenhaut, Pierre Bernard, Valérie Race, Yves SznajerAbstractAntenatal diagnosis of cardio-facio-cutaneous syndrome: prenatal characteristics and contribution of fetal facial dysmorphic signs in utero. This paper is a case study and review of literature.“RASopathies” is the term coined for a group of genetic diseases that share modulation inside the MAPKinase pathway. Mutations inside the coding sequence of any of these genes may be responsible for the upregula...
Source: European Journal of Obstetrics and Gynecology and Reproductive Biology - July 17, 2019 Category: OBGYN Source Type: research
Antenatal diagnosis of cardio-facio-cutaneous syndrome: prenatal characteristics and contribution of fetal facial dysmorphic signs in utero. About a case and review of literature
Antenatal diagnosis of cardio-facio-cutaneous syndrome: prenatal characteristics and contribution of fetal facial dysmorphic signs in utero. This paper is a case study and review of literature. “RASopathies” is the term coined for a group of genetic diseases that share modulation inside the MAPKinase pathway. Mutations inside the coding sequence of any of these genes may be responsible for the upregulation of the RAS pathway, leading on the clinical level to Type 1 Neurofibromatosis (N F1), Noonan syndrome (NS), Costello syndrome (CS), Multiple Lentigines, Loose Anagen Hair syndrome, Cardio-Facio-Cutaneous syndrome (CF...
Source: European Journal of Obstetrics, Gynecology, and Reproductive Biology - July 15, 2019 Category: OBGYN Authors: Jean-Marc Biard, Patricia Steenhaut, Pierre Bernard, Val érie Race, Yves Sznajer Tags: Review article Source Type: research
Anesthetic Management in an Adult Patient With Costello Syndrome: A Case Report
Costello syndrome is a rare genetic disorder characterized by mental and growth retardation and distinctive coarse facies. A significant proportion of patients with Costello syndrome have hypertrophic cardiomyopathy, papillomata, and malignant tumors. General anesthesia practice, especially airway and cardiac management, in patients with Costello syndrome may be complicated by anatomical features and cardiac abnormalities. There have been several reports on the anesthetic management of children with Costello syndrome, but few have reported on the anesthetic management of adults with Costello syndrome. In adults, careful pr...
Source: A&A Case Reports - July 15, 2019 Category: Anesthesiology Tags: Case Reports Source Type: research
Pathogenesis of Growth Failure in Rasopathies.
Authors: Aftab S, Dattani MT
Abstract
The RASopathies are a group of developmental genetic syndromes that are caused by germline mutations in genes encoding proteins of the Ras-Mitogen-Activated Protein kinase (RAS-MAPK) pathway. RASopathies include Noonan Syndrome (NS), Neurofibromatosis Type 1 (NF1), Noonan syndrome with multiple lentigines (NSML/LEOPARD), Costello syndrome (CS), Cardio-facio-cutaneous syndrome (CFC), capillary malformation-arteriovenous malformation syndrome (CM-AVM) and Legius Syndrome. These syndromes have many overlapping features; however, the most persistent feature common to all i...
Source: Pediatric Endocrinology Reviews - May 24, 2019 Category: Endocrinology Tags: Pediatr Endocrinol Rev Source Type: research
Clinical Manifestations of Noonan Syndrome and Related Disorders.
Authors: Breilyn MS, Mehta L
Abstract
Noonan syndrome represents a heterogeneous group of genetic disorders caused by mutations in genes of the RAS/MAPK pathway. Related syndromes include cardiofaciocutaneous syndrome, Noonan syndrome with multiple lentigines and Costello syndrome. The common phenotypic features of Noonan syndrome include facial dysmorphisms, short stature, congenital heart defects and genitourinary abnormalities. These and other findings as well as features of related disorders are discussed. In addition we briefly review clinical diagnosis and prenatal findings of these syndromes and gen...
Source: Pediatric Endocrinology Reviews - May 24, 2019 Category: Endocrinology Tags: Pediatr Endocrinol Rev Source Type: research
Functional robustness of adult spermatogonial stem cells after induction of hyperactive < i > Hras < /i >
In this study, we created a lineage tracing system, which enabled undifferentiated spermatogonia with endogenous expression ofHrasG12V, a known pathogenic gain-of-function mutation in RAS-MAPK signaling, to compete with their wild-type counterparts in the mouse testis. Over a year of fate analysis, neitherHrasG12V-positive germ cells nor sperm exhibited a significant expansion compared to wild-type neighbors. Short-term stem cell capacity as measured by transplantation analysis was also comparable between wild-type and mutant groups. Furthermore, although constitutively active HRAS was detectable in the mutant cell lines, ...
Source: PLoS Genetics - May 2, 2019 Category: Genetics & Stem Cells Authors: Makiko Yamada Source Type: research
Noonan Syndrome in South Africa: Clinical and Molecular Profiles
Conclusion
This first application of targeted NGS for the molecular diagnosis of NS in South Africans suggests that clinical characteristics and genotype-phenotype correlations found in affected individuals are generally similar to those reported in other populations. Therefore, careful phenotyping based on existing diagnostic criteria can effectively enable the diagnosis of most NS-affected individuals in South Africa. The use of targeted NGS in the present study have allowed for detection of novel variants in genes infrequently associated with NS in other populations. Further studies of a larger African cohort with NS, ...
Source: Frontiers in Genetics - April 15, 2019 Category: Genetics & Stem Cells Source Type: research
