scholarly journals Noonan syndrome with multiple lentigines and associated craniosynostosis

2018 ◽  
Vol 43 (3) ◽  
pp. 357-359 ◽  
Author(s):  
B. S. McDonald ◽  
M. Pigors ◽  
D. P. Kelsell ◽  
E. A. O'Toole ◽  
E. Burkitt-Wright ◽  
...  
Keyword(s):  
Noonan Syndrome ◽  
Multiple Lentigines

Widespread keratosis pilaris in a patient with Noonan syndrome with multiple lentigines

2018 ◽  
Vol 57 (11) ◽  
pp. e140-e141
Author(s):  
Seda Purnak ◽  
Vehap Topçu ◽  
Büşranur Çavdarlı ◽  
Elçin Kadan ◽  
Başak Yalçın
Keyword(s):  
Noonan Syndrome ◽  
Multiple Lentigines

scholarly journals Elevated Ca2+ transients and increased myofibrillar power generation cause cardiac hypercontractility in a model of Noonan syndrome with multiple lentigines

2015 ◽  
Vol 308 (9) ◽  
pp. H1086-H1095 ◽  
Author(s):  
Sarah A. Clay ◽  
Timothy L. Domeier ◽  
Laurin M. Hanft ◽  
Kerry S. McDonald ◽  
Maike Krenz
Keyword(s):  
Noonan Syndrome ◽  
Tyrosine Phosphatase ◽  
Severe Form ◽  
Cellular Mechanisms ◽  
Specific Expression ◽  
Plasmic Reticulum ◽  
Power Load ◽  
Intracellular Ca ◽  
Generating Capacity ◽  
Multiple Lentigines

Noonan syndrome with multiple lentigines (NSML) is primarily caused by mutations in the nonreceptor protein tyrosine phosphatase SHP2 and associated with congenital heart disease in the form of pulmonary valve stenosis and hypertrophic cardiomyopathy (HCM). Our goal was to elucidate the cellular mechanisms underlying the development of HCM caused by the Q510E mutation in SHP2. NSML patients carrying this mutation suffer from a particularly severe form of HCM. Drawing parallels to other, more common forms of HCM, we hypothesized that altered Ca2+ homeostasis and/or sarcomeric mechanical properties play key roles in the pathomechanism. We used transgenic mice with cardiomyocyte-specific expression of Q510E-SHP2 starting before birth. Mice develop neonatal onset HCM with increased ejection fraction and fractional shortening at 4–6 wk of age. To assess Ca2+ handling, isolated cardiomyocytes were loaded with fluo-4. Q510E-SHP2 expression increased Ca2+ transient amplitudes during excitation-contraction coupling and increased sarcoplasmic reticulum Ca2+ content concurrent with increased expression of sarco(endo)plasmic reticulum Ca2+-ATPase. In skinned cardiomyocyte preparations from Q510E-SHP2 mice, force-velocity relationships and power-load curves were shifted upward. The peak power-generating capacity was increased approximately twofold. Transmission electron microscopy revealed that the relative intracellular area occupied by sarcomeres was increased in Q510E-SHP2 cardiomyocytes. Triton X-100-based myofiber purification showed that Q510E-SHP2 increased the amount of sarcomeric proteins assembled into myofibers. In summary, Q510E-SHP2 expression leads to enhanced contractile performance early in disease progression by augmenting intracellular Ca2+ cycling and increasing the number of power-generating sarcomeres. This gives important new insights into the cellular pathomechanisms of Q510E-SHP2-associated HCM.

scholarly journals Growth patterns of patients with Noonan syndrome: correlation with age and genotype

2016 ◽  
Vol 174 (5) ◽  
pp. 641-650 ◽  
Author(s):  
Catie Cessans ◽  
Virginie Ehlinger ◽  
Catherine Arnaud ◽  
Armelle Yart ◽  
Yline Capri ◽  
...  
Keyword(s):  
Body Mass Index ◽  
Noonan Syndrome ◽  
Growth Parameters ◽  
Standard Deviation Score ◽  
Growth Patterns ◽  
Healthy Population ◽  
Length Standard ◽  
Study Population ◽  
Multiple Lentigines

Background Growth patterns of patients with Noonan syndrome (NS) were established before the involved genes were identified. Objective The goal of this study was to compare growth parameters according to genotype in patients with NS. Subjects and methods The study population included 420 patients (176 females and 244 males) harboring mutations in the PTPN11, SOS1, RAF1, or KRAS genes. NS-associated PTPN11 mutations (NS-PTPN11) and NS with multiple lentigines-associated PTPN11 mutations (NSML-PTPN11) were distinguished. Birth measures and height and body mass index (BMI) measures at 2, 5, 10 years, and adulthood were compared with the general population and between genotypes. Results Patients with NS were shorter at birth (mean birth length standard deviation score (SDS): –1.0 ± 1.4; P < 0.001) and throughout childhood than the healthy population, with height SDS being –2.1 ± 1.3 at 2 years, and –2.1 ± 1.2 at 5 and 10 years and adulthood (P < 0.001). At birth, patients with NS-PTPN11 were significantly shorter and thinner than patients with NSML-PTPN11, SOS1, or KRAS. Growth retardation was significantly less severe and less frequent at 2 years in patients with NSML-PTPN11 and SOS1 than in patients with NS-PTPN11 (P < 0.001 and P = 0.002 respectively). Patients with NS had lower BMI at 10 years (P < 0.001). No difference between genotypes was demonstrated. Conclusion Determining the growth patterns of patients with NS according to genotype should better inform clinicians about the natural course of growth in NS so that they can optimize the follow-up and management of these patients.

scholarly journals Assessing the Gene-Disease Association of 19 Genes with the RASopathies using the ClinGen Gene Curation Framework

2018 ◽  
Author(s):  
Andrew Grant ◽  
Brandon Cushman ◽  
Hélène Cavé ◽  
Mitchell W. Dillon ◽  
Bruce D. Gelb ◽  
...  
Keyword(s):  
Noonan Syndrome ◽  
Expert Panel ◽  
Disease Association ◽  
Costello Syndrome ◽  
Ministry Of Education ◽  
Genome Research ◽  
National Human ◽  
Anagen Hair ◽  
Multiple Lentigines ◽  
Literature Curation

AbstractThe RASopathies are a complex group of diseases regarding phenotype and genetic etiology. The ClinGen RASopathy Expert Panel assessed published and other publicly available evidence supporting the association of 19 genes with RASopathy conditions. Using the semi-quantitative literature curation method developed by the ClinGen Gene Curation Working Group, evidence for each gene was curated and scored for Noonan syndrome, Costello syndrome, cardiofaciocutaneous (CFC) syndrome, Noonan syndrome with multiple lentigines (NSML), and Noonan-like syndrome with loose anagen hair (NS/LAH).The curated evidence supporting each gene-disease relationship was then discussed and approved by the ClinGen RASopathy Expert Panel. Each association’s strength was classified as Definitive, Strong, Moderate, Limited, Disputed, or No Evidence. Eleven genes were classified as definitively associated with at least one RASopathy condition. Two genes classified as strong for association with at least one RASopathy condition while one gene was moderate and three were limited. The RAS EP also refuted the association of two genes for a RASopathy condition. Overall, our results provide a greater understanding of the different gene-disease relationships within the RASopathies and can help guide and direct clinicians, patients and researchers who are identifying variants in individuals with a suspected RASopathyGRANT NUMBERS:Research reported in this publication was supported by the National Human Genome Research Institute (NHGRI) under award number U41HG006834. MZ received support from German Federal Ministry of Education and Research (BMBF): NSEuroNet (FKZ 01GM1602A), GeNeRARe (FKZ 01GM1519A).

Cochlear implantation and clinical features in patients with Noonan syndrome and Noonan syndrome with multiple lentigines caused by a mutation in PTPN11

2017 ◽  
Vol 97 ◽  
pp. 228-234 ◽  
Author(s):  
Josephine W.I. van Nierop ◽  
Dorothée C. van Trier ◽  
Ineke van der Burgt ◽  
Jos M.T. Draaisma ◽  
Emmanuel A.M. Mylanus ◽  
...  
Keyword(s):  
Clinical Features ◽  
Cochlear Implantation ◽  
Noonan Syndrome ◽  
Multiple Lentigines
Sign in / Sign up

Export Citation Format

Share Document