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تعداد آیتم قابل مشاهده باقیمانده : 1 مورد

Noonan syndrome genes: Frequency estimate and genotype-phenotype correlation

Noonan syndrome genes: Frequency estimate and genotype-phenotype correlation
Gene Phenotype Percent[1] Genotype-phenotype correlation
PTPN11 NS 50 Classical NS. Highest incidence of pulmonary valve stenosis, atrial septal defects.
NS with increased risk of JMML   Specific mutations.
NSML   Specific mutations. Usually normal intellect.
SOS1[2] NS 11 Less short stature and intellectual disability. Dry skin common.
SOS2 Classical NS   Similar to SOS1 phenotype, but lymphatic anomalies may be prevalent.
RAF1[3] NS, but variable 5 Hypertrophic cardiomyopathy common (95%); may be neonatal. Pediatric dilated cardiomyopathy. Pulmonary artery hypertension. Lentigines (NSML) reported.
RIT1[4] NS, but variable 5 Normal growth, skin, and intellect. High incidence of cardiac abnormalities, including atrial tachyarrhythmia. Hypertrophic cardiomyopathy common; may be neonatal. Lymphatic complications common, including prenatal. May have small increased malignancy risk.
LZTR1[5]  NS, variable from mild to lethal fetal hydrops 10  Lymphatic anomalies and hypertrophic cardiomyopathy prevalent amongst individuals with autosomal-recessive LZTR1-associated NS. Autosomal-dominant forms are frequently milder.
NRAS[6] Classical NS 0.2  
RRAS, RRAS2 Classical NS    
MRAS NS   Hypertrophic cardiomyopathy.
SHOC2[7] NS with loose anagen hair 2 Sparse hair, hyperpigmented skin, eczema, keratosis pilaris. Nasal voice. Growth hormone deficiency common.
CBL[8] NS, but variable, often subtle manifestations   Increased risk of JMML. Moyamoya disease reported.
PPP1CB[9] SHOC2-like    
KRAS Some NS/CFC 1.5 Intellectual disability more common.
BRAF Some NS/CFC <2 Skin and hair differences more common. More intellectual disability. NSML reported.
MAP2K1 Rare NS/CFC <2  
PTPN11: protein tyrosine phosphatase, nonreceptor type 11; NS: Noonan syndrome; JMML: juvenile myelomonocytic leukemia; NSML: Noonan syndrome with multiple lentigines; SOS1: SOS Ras/Rac guanine nucleotide exchange factor 1; SOS2: SOS Ras/Rho guanine nucleotide exchange factor 2; RAF1: Raf-1 proto-oncogene, serine/threonine kinase; RIT1: Ric-like protein without CAAX motif 1; LZTR1: leucine zipper-like transcription regulator 1; NRAS: NRAS proto-oncogene, GTPase; RRAS: related RAS viral oncogene homolog; MRAS: muscle RAS viral oncogene homolog; SHOC2: SHOC2, leucine rich repeat scaffold protein; CBL: Cbl proto-oncogene; PPP1CB: protein phosphatase 1 catalytic subunit beta; KRAS: KRAS proto-oncogene, GTPase; CFC: cardio-facio-cutaneous syndrome; BRAF: B-Raf proto-oncogene, serine/threonine kinase; MAP2K1: mitogen-activated protein kinase kinase 1.
References:
  1. Aoki Y, Niihori T, Inoue S, Matsubara Y. Recent advances in RASopathies. J Hum Genet 2016; 61:33.
  2. Lepri F, De Luca A, Stella L, et al. SOS1 mutations in Noonan syndrome: Molecular spectrum, structural insights on pathogenic effects, and genotype–phenotype correlations. Hum Mutat 2011; 32:760.
  3. Razzaque MA, Nishizawa T, Komoike Y, et al. Germline gain-of-function mutations in RAF1 cause Noonan syndrome. Nat Genet 2007; 39:1013.
  4. Bertola DR, Yamamoto GL, Almeida TF, et al. Further evidence of the importance of RIT1 in Noonan syndrome. Am J Med Genet A 2014; 164A:2952.
  5. Johnston JJ, van der Smagt JJ, Rosenfeld JA, et al. Autosomal recessive Noonan syndrome associated with biallelic LZTR1 variants. Genet Med 2018; 20:1175
  6. Altmüller F, Lissewski C, Bertola D, et al. Genotype and phenotype spectrum of NRAS germline variants. Eur J Hum Genet 2017; 25:823.
  7. Gripp KW, Zand DJ, Demmer L, et al. Expanding the SHOC2 mutation associated phenotype of Noonan syndrome with loose anagen hair: Structural brain anomalies and myelofibrosis. Am J Med Genet A 2013; 161A:2420.
  8. Martinelli S, De Luca A, Stellacci E, et al. Heterozygous germline mutations in the CBL tumor-suppressor gene cause a Noonan syndrome-like phenotype. Am J Hum Genet 2010; 87:250.
  9. Gripp KW, Aldinger KA, Bennett JT, et al. A novel rasopathy caused by recurrent de novo missense mutations in PPP1CB closely resembles Noonan syndrome with loose anagen hair. Am J Med Genet A 2016; 170:2237.
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