Objective studies of the face of Noonan, Cardio‐facio‐cutaneous, and Costello syndromes: A comparison of three disorders of the Ras/MAPK signaling pathway
In this study, subjective observations, in the main, were validated by anthropometry with one exception. In individuals with Costello syndrome, mouth width was normal, thus the impression of wide mouth is likely due to full lips or the mouth being viewed in relation to a narrow lower face. When the three conditions were compared objectively, syndrome‐specific pattern profiles showed high concordance in early life. At older ages, Cardio‐facio‐cutaneous syndrome was distinguished by increased width of the mid/lower face, and reduced growth of maxillary and mandibular dimensions was noted in both Noonan and Costello syn...
Source: American Journal of Medical Genetics Part A - April 30, 2016 Category: Genetics & Stem Cells Authors: Judith E. Allanson Tags: Original Article Source Type: research
Respiratory system involvement in Costello syndrome
Costello syndrome (CS) is a multisystem disorder caused by heterozygous germline mutations in the HRAS proto‐oncogene. Respiratory system complications have been reported in individuals with CS, but a comprehensive description of the full spectrum and incidence of respiratory symptoms in these patients is not available. Here, we report the clinical course of four CS patients with respiratory complications as a major cause of morbidity. Review of the literature identified 56 CS patients with descriptions of their neonatal course and 17 patients in childhood/adulthood. We found that in the neonatal period, respiratory comp...
Source: American Journal of Medical Genetics Part A - April 21, 2016 Category: Genetics & Stem Cells Authors: Natalia Gomez‐Ospina, Christin Kuo, Amitha Lakshmi Ananth, Angela Myers, Marie‐Luise Brennan, David A. Stevenson, Jonathan A. Bernstein, Louanne Hudgins Tags: Original Article Source Type: research
RASopathies: Presentation at the Genome, Interactome, and Phenome Levels
Clinical symptoms often reflect molecular correlations between mutated proteins. Alignment between interactome and phenome levels reveals new disease genes and connections between previously unrelated diseases. Despite a great potential for novel discoveries, this approach is still rarely used in genomics. In the present study, we analyzed the data of 6 syndromes belonging to the RASopathy class of disorders (RASopathies) and presented them as a model to study associations between genome, interactome, and phenome levels. Causative genes and clinical symptoms were collected from OMIM and NCBI GeneReviews databases for 6 syn...
Source: Molecular Syndromology - April 20, 2016 Category: Molecular Biology Source Type: research
Lymphodysplasia and kras mutation: a case report and literature review.
We describe the clinical data of one case of CFC syndrome, genetically determined by KRAS mutation, that involved chylothorax, lymphedema, sinus pericranii, craniosynostosis, and seizures. This is the second case report of the literature.
PMID: 26939159 [PubMed - in process] (Source: Lymphology)
Source: Lymphology - March 6, 2016 Category: Internal Medicine Tags: Lymphology Source Type: research
An uncommon condition may provide insight into a common problem
Our understanding of genetic syndromes continues to grow, including those of the large group called RASopathies. These clinical syndromes have some phenotypic overlap and include Noonan syndrome, neurofibromatosis type 1, cardio-facio-cutaneous syndrome, and Costello syndrome. Although the conditions are varied, all of these syndromes are caused by germline mutations in genes related to components of or regulation of the RAS/MAPK pathways. These signal transduction pathways control cell proliferation, differentiation, and survival. (Source: The Journal of Pediatrics)
Source: The Journal of Pediatrics - February 25, 2016 Category: Pediatrics Authors: Denise M. Goodman Tags: The Editors' Perspectives Source Type: research
Prenatal findings of hypertrophic cardiomyopathy in a severe case of Costello syndrome
(Source: Ultrasound in Obstetrics and Gynecology)
Source: Ultrasound in Obstetrics and Gynecology - February 25, 2016 Category: Radiology Authors: Ryo Uemura, Daisuke Tachibana, Yasushi Kurihara, Ritsuko K. Pooh, Yoko Aoki, Masayasu Koyama Tags: Letter to the Editor Source Type: research
Prenatal findings of hypertrophic cardiomyopathy in a severe case of Costello syndrome.
PMID: 26916728 [PubMed - as supplied by publisher] (Source: The Ultrasound Review of Obstetrics and Gynecology)
Source: The Ultrasound Review of Obstetrics and Gynecology - February 25, 2016 Category: Radiology Authors: Uemura R, Tachibana D, Kurihara Y, Pooh RK, Aoki Y, Koyama M Tags: Ultrasound Obstet Gynecol Source Type: research
The rare costello variant HRAS c.173C>T (p.T58I) with severe neonatal hypertrophic cardiomyopathy
We report a 10‐year‐old girl presenting with severe neonatal hypertrophic cardiomyopathy (HCM), feeding difficulties, mildly abnormal facial features, and progressive skeletal muscle symptoms but with normal cognitive development. Targeted oligonucleotide‐selective sequencing of 101 cardiomyopathy genes revealed the genetic diagnosis, and the mutation was verified by Sanger sequencing in the patient and her parents. To offer insights into the potential mechanism of patient mutation, protein structural analysis was performed using the resolved structure of human activated HRAS protein with bound GTP analogue (PDB id 5...
Source: American Journal of Medical Genetics Part A - February 18, 2016 Category: Genetics & Stem Cells Authors: Anita Hiippala, Catalina Vasilescu, Jonna Tallila, Tero‐Pekka Alastalo, Anders Paetau, Tiina Tyni, Anu Suomalainen, Liliya Euro, Tiina Ojala Tags: Original Article Source Type: research
Acute lymphoblastic leukemia in the context of rasopathies.
Abstract
Noonan syndrome is associated with a range of malignancies including acute lymphoblastic leukemia (ALL). However, little information is available regarding the frequency, natural history, characteristics and prognosis of ALL in Noonan syndrome or RASopathies in general. Cross-referencing data from a large prospective cohort of 1176 patients having a molecularly confirmed RASopathy with data from the French childhood cancer registry allowed us to identify ALL in 6 (0.5%) patients including 4/778 (0.5%) with a germline PTPN11 mutation and 2/94 (2.1%) with a germline SOS1 mutation. None of the patien...
Source: European Journal of Medical Genetics - February 4, 2016 Category: Genetics & Stem Cells Authors: Cavé H, Caye A, Strullu M, Aladjidi N, Vignal C, Ferster A, Méchinaud F, Domenech C, Pierri F, Contet A, Cacheux V, Irving J, Kratz C, Clavel J, Verloes A Tags: Eur J Med Genet Source Type: research
Recombinant growth hormone therapy in a girl with costello syndrome: a 4-year observation
Conclusions:
The possibility of growth hormone (GH) treatment can be considered in cases of documented GH deficiency in patients with Costello syndrome, but only under close oncologic and cardiologic supervision. (Source: Italian Journal of Pediatrics)
Source: Italian Journal of Pediatrics - January 26, 2016 Category: Pediatrics Authors: Ewa BlachowskaEl¿bieta PetriczkoAnita Horodnicka-JózwaAgata SkórkaMagdalena PelcMa¿gorzata Krajewska-WalasekMieczys¿aw Walczak Source Type: research
Recombinant growth hormone therapy in a girl with costello syndrome: a 4-year observation
Conclusions
The possibility of growth hormone (GH) treatment can be considered in cases of documented GH deficiency in patients with Costello syndrome, but only under close oncologic and cardiologic supervision. (Source: Italian Journal of Pediatrics)
Source: Italian Journal of Pediatrics - January 26, 2016 Category: Pediatrics Source Type: research
Understanding Growth Failure in Costello Syndrome: Increased Resting Energy Expenditure
This study documents that individuals with Costello syndrome have increased resting energy expenditure. We speculate this could be one of the potential mechanisms causing failure to thrive. (Source: The Journal of Pediatrics)
Source: The Journal of Pediatrics - January 9, 2016 Category: Pediatrics Authors: Chiara Leoni, Roberta Onesimo, Valentina Giorgio, Antonella Diamanti, Daniela Giorgio, Lucilla Martini, Aurora Rossodivita, Marco Tartaglia, Giuseppe Zampino Tags: Clinical and Laboratory Observations Source Type: research
Polymerase {zeta} Activity Is Linked to Replication Timing in Humans: Evidence from Mutational Signatures
This study uncovers the genomic preferences of pol , shedding light on a novel cause of mutational heterogeneity along the genome. (Source: Molecular Biology and Evolution)
Source: Molecular Biology and Evolution - November 19, 2015 Category: Molecular Biology Authors: Seplyarskiy, V. B., Bazykin, G. A., Soldatov, R. A. Tags: Discoveries Source Type: research
Rasopathies - dysmorphic syndromes with short stature and risk of malignancy.
CONCLUSION: Despite the overlapping clinical features, Rasopathy syndromes exhibit unique fenotypical features and the precise molecular diagnostics may lead to confirmation of each syndrome. The molecular diagnostics may allow the detection of pathogenic mutation associated with tumorigenesis.
PMID: 24156711 [PubMed - indexed for MEDLINE] (Source: Endocrine Regulations)
Source: Endocrine Regulations - November 18, 2015 Category: Endocrinology Tags: Endocr Regul Source Type: research
Paternal uniparental disomy 11p15.5 in the pancreatic nodule of an infant with Costello syndrome: Shared mechanism for hyperinsulinemic hypoglycemia in neonates with Costello and Beckwith–Wiedemann syndrome and somatic loss of heterozygosity in Costello syndrome driving clonal expansion
Costello syndrome (CS) entails a cancer predisposition and is caused by activating HRAS mutations, typically arising de novo in the paternal germline. Hypoglycemia is common in CS neonates. A previously reported individual with the rare HRAS p.Gln22Lys had hyperinsulinemic hypoglycemia. Autopsy showed a discrete pancreatic nodule. The morphologic and immunohistochemistry findings, including loss of p57Kip2 protein, were identical to a focal lesion of congenital hyperinsulinism, however, no KCNJ11 or ABCC8 mutation was identified and germline derived DNA showed no alternation of the maternal or paternal 11p15 alleles. Here ...
Source: American Journal of Medical Genetics Part A - November 18, 2015 Category: Genetics & Stem Cells Authors: Karen W. Gripp, Katherine M. Robbins, Brandon S. Sheffield, Anna F. Lee, Millan S. Patel, Stephen Yip, Daniel Doyle, Deborah Stabley, Katia Sol‐Church Tags: Research Article Source Type: research
