Noonan syndrome-causing genes

Bouchikhi, Ihssane El; Belhassan, Khadija; Moufid, Fatima Zohra; Houssaini, Mohammed Iraqui; Bouguenouch, Laila; Samri, Imane; Atmani, S.; Ouldim, Karim

doi:10.1016/j.ijpam.2016.06.003

Cited by 67 publications

(63 citation statements)

References 110 publications

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“… CFC, Cardiofaciocutaneous syndrome; NSML, Noonan syndrome with multiple lentigenes; Table compiled from (51, 52) and GeneReviews. …”

Section: Tablementioning

confidence: 99%

Genetics of paediatric cardiomyopathies

Ware

2017

Current Opinion in Pediatrics

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Purpose of review Pediatric cardiomyopathy is a rare disease with a genetic basis. The purpose of this review is to discuss the current status of genetic findings in the pediatric cardiomyopathy population and present recent progress in utilizing this information for management and therapy. Recent findings With increased clinical genetic testing, an understanding of the genetic causes of cardiomyopathy is improving and novel causes are identified. Recent progress in identifying the scope of genetic variation in large population datasets has led to reassessment and refinement of our understanding of the significance of rare genetic variation. As a result, the stringency of variant interpretation has increased, at times leading to revision of previous mutation results. Transcriptome and epigenome studies are elucidating important pathways for disease progression and highlight similarities and differences from adult cardiomyopathy. Therapy targeted toward the underlying cause of cardiomyopathy is emerging for a number of rare syndromes such as Pompe and Noonan syndromes, and genome editing and induced pluripotent stem cells provide promise for additional precision medicine approaches. Summary Genetics is moving at a rapid pace in pediatric cardiomyopathy. Genetic testing is increasingly being incorporated into clinical care. While challenges in interpretation of rare genetic variation remains challenging, the opportunity to provide management and therapy targeted toward the underlying genetic cause is beginning to be realized.

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“… CFC, Cardiofaciocutaneous syndrome; NSML, Noonan syndrome with multiple lentigenes; Table compiled from (51, 52) and GeneReviews. …”

Section: Tablementioning

confidence: 99%

Genetics of paediatric cardiomyopathies

Ware

2017

Current Opinion in Pediatrics

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“…We have sequenced seven exons (2,3,4,7,8,12,13) that were proved earlier to host 99.9% of PTPN11 mutations [3], which means that about 1% of mutations might be overlooked in this study. Three of detected mutations (D61G, Y63C, and A72S) are clustered in the most mutated exon (exon 3).…”

Section: Molecular and Functional Prediction Findingmentioning

confidence: 98%

“…RASopathies are mainly caused by mutations in RAS-MAP kinase (rat sarcoma viral oncogene homolog/mitogen-activated protein kinases) pathway genes. The most involved genes are PTPN11, SOS1, RAF1, KRAS, BRAF, NRAS, HRAS, SHOC2, CBL, and MEK1 159 [2,3].…”

Section: Introductionmentioning

confidence: 99%

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Molecular and environmental characterization of Noonan syndrome in Morocco reveals a significant association with consanguinity and advanced parental age

Bouchikhi

Bouguenouch

Moufid

et al. 2020

Egypt J Med Hum Genet

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Background: Noonan syndrome (NS) is one of the most common RASopathies, with an autosomal dominant inheritance. This disorder is caused by a range of genes belonging to the RAS-MAP kinase (rat sarcoma viral oncogene homolog/mitogen-activated protein kinases) pathway, with PTPN11 (protein-tyrosine phosphatase, nonreceptor type 11) being the most involved genetic factor. The aim of this study is to report PTPN11 mutations found in a cohort of Moroccans with Noonan syndrome, compare the mutation rate with various studies, and statistically assess involvement of prominent risk factors in manifestation of this disorder. Thirty-one NS patients were screened for PTPN11 mutations using PCR-Sanger sequencing method. Pathogenic effect prediction, for detected variants, was carried out using PROVEAN, MutationTaster2, and HSF programs. Statistical tests were performed with R software. Chi-square and Fisher's exact tests were used in percentage comparisons, while Student's test was used in average comparisons. Results: We detected five pathogenic mutations, one synonymous variant with a potential altering effect on splicing function, and three novel intronic duplications. PTPN11 mutation rate in our cohort is around 16.13%. Comparison of this rate with the corresponding rates in various populations shows notably significant differences across continents. Conclusions: Besides genetic factors, the present study suggests involvement of additional environmental factors. Statistical assessment of clinical data confirms particularly the association of NS manifestation with consanguinity and advanced paternal age, and suggests an eventual implication of advanced maternal age as well.

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“…Cardiac involvement is present in 80%-90% of individuals. The most common cardiovascular findings are PS in 50%-60% and hypertrophic cardiomyopathy (HCM) in 20% (Marino et al 1999;El Bouchikhi et al 2016;Jhang et al 2016). The presence of HCM contributes to significant mortality and tends to be earlier-onset and more rapidly progressive than other types of pediatric HCM (Wilkinson et al 2012;Gelb et al 2015).…”

Section: Noonan Syndrome and Rasopathiesmentioning

confidence: 99%

Genetic Basis of Human Congenital Heart Disease

Nees¹,

Chung

2019

Cold Spring Harb Perspect Biol

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Congenital heart disease (CHD) is the most common major congenital anomaly with an incidence of ∼1% of live births and is a significant cause of birth defect-related mortality. The genetic mechanisms underlying the development of CHD are complex and remain incompletely understood. Known genetic causes include all classes of genetic variation including chromosomal aneuploidies, copy number variants, and rare and common singlenucleotide variants, which can be either de novo or inherited. Among patients with CHD, ∼8%-12% have a chromosomal abnormality or aneuploidy, between 3% and 25% have a copy number variation, and 3%-5% have a single-gene defect in an established CHD gene with higher likelihood of identifying a genetic cause in patients with nonisolated CHD. These genetic variants disrupt or alter genes that play an important role in normal cardiac development and in some cases have pleiotropic effects on other organs. This work reviews some of the most common genetic causes of CHD as well as what is currently known about the underlying mechanisms. C ongenital heart disease (CHD) is the most common major congenital anomaly with an incidence of ∼1% of live births (Hoffman and Kaplan 2002; Calzolari et al. 2003). CHD is a significant cause of birth defect-related mortality (

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Noonan syndrome-causing genes

Cited by 67 publications

References 110 publications

Genetics of paediatric cardiomyopathies

Genetics of paediatric cardiomyopathies

Molecular and environmental characterization of Noonan syndrome in Morocco reveals a significant association with consanguinity and advanced parental age

Genetic Basis of Human Congenital Heart Disease

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