We performed the genetic analysis of Rasopathy syndromes in patients from Central European by direct sequencing followed by next generation sequencing of genes associated with Rasopathies. All 51 patients harboured the typical features of Rasopathy syndromes. Thirty-five mutations were identified in the examined patients (22 in PTPN11, two in SOS1, one in RIT1, one in SHOC2, two in HRAS, three in BRAF, two in MAP2K1 and two in the NF1 gene). Two of them (p.Gly392Glu in the BRAF gene and p.Gln164Lys in the MAP2K1 gene) were novel with a potentially pathogenic effect on the structure of these proteins. Statistically significant differences in the presence of pulmonary stenosis (63.64% vs. 23.81%, P = 0.013897) and cryptorchidism (76.47% vs. 30%, P = 0.040224) were identified as the result of comparison of the prevalence of phenotypic features in patients with the phenotype of Noonan syndrome and mutation in the PTPN11 gene, with the prevalence of the same features in patients without PTPN11 mutation. Cryptorchidism as a statistically significant feature in our patients with PTPN11 mutation was not reported as significant in other European countries (Germany, Italy and Greece). The majority of mutations were clustered in exons 3 (45.45%), 8 (22.73%), and 13 (22.73%) of the PTPN11 gene.

• Klíčová slova
• BRAF, MAP2K1, PTPN11, Rasopathies, cardio-facio-cutaneous syndrome, central Europe, noonan syndrome,
• MeSH
• běloši genetika   MeSH
• dítě MeSH
• dospělí MeSH
• ektodermální dysplazie genetika   MeSH
• exony MeSH
• faciální stigmatizace MeSH
• fenotyp MeSH
• intracelulární signální peptidy a proteiny genetika   MeSH
• kojenec MeSH
• kryptorchismus genetika   MeSH
• lidé MeSH
• mladiství MeSH
• mladý dospělý MeSH
• mutační analýza DNA * MeSH
• neprospívání genetika   MeSH
• Noonanové syndrom genetika   MeSH
• předškolní dítě MeSH
• protein SOS1 genetika   MeSH
• Ras proteiny genetika   MeSH
• stenóza pulmonální chlopně genetika   MeSH
• tyrosinfosfatasa nereceptorového typu 11 genetika   MeSH
• vrozené srdeční vady genetika   MeSH
• Check Tag
• dítě MeSH
• dospělí MeSH
• kojenec MeSH
• lidé MeSH
• mladiství MeSH
• mladý dospělý MeSH
• mužské pohlaví MeSH
• předškolní dítě MeSH
• ženské pohlaví MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH
• Názvy látek
• intracelulární signální peptidy a proteiny MeSH
• protein SOS1 MeSH
• PTPN11 protein, human MeSH Prohlížeč
• Ras proteiny MeSH
• RIT1 protein, human MeSH Prohlížeč
• SHOC2 protein, human MeSH Prohlížeč
• tyrosinfosfatasa nereceptorového typu 11 MeSH

Noonan-like syndrome with loose anagen hair (NS/LAH; OMIM 607721) due to a missense mutation c.4A>G in SHOC2 predicting p.Ser2Gly has been described recently. This condition is characterized by facial features similar to Noonan syndrome, reduced growth, cardiac defects, and typical abnormal hair. We report on a patient with molecularly confirmed NS/LAH with coarctation of the aorta. The girl was precipitously born at 37 weeks of gestation at home and required a 3-min resuscitation. Increased nuchal translucency and aortic coarctation with a small ventricular septal defect were described prenatally, hypertrophic cardiomyopathy was detected postnatally. The patient presented with facial dysmorphism typical of NS with redundant skin over the nape and on the back. Short stature, relative macrocephaly, failure-to-thrive together with dystrophic appearance, developmental delay mainly in motor milestones and very thin, sparse, slow-growing hair occurred a few weeks after birth. Endocrine evaluation revealed low IGF-1 levels and borderline growth hormone deficiency. Growth hormone therapy started at 16 months had a partial effect and prevented further growth deterioration. Coarctation of the aorta is not a typical heart defect among individuals with NS/LAH, therefore our observation extends the phenotypic spectrum of this disorder.

• Klíčová slova
• Noonan-like syndrome with loose anagen hair, RASopathies, SHOC2, coarctation of the aorta,
• MeSH
• faciální stigmatizace MeSH
• fenotyp * MeSH
• intracelulární signální peptidy a proteiny genetika   MeSH
• koarktace aorty diagnóza   MeSH
• kojenec MeSH
• lidé MeSH
• lidský růstový hormon terapeutické užití   MeSH
• mutace MeSH
• Noonanové syndrom diagnóza   farmakoterapie   genetika   MeSH
• růstové grafy MeSH
• syndrom ztráty anagenních vlasů diagnóza   farmakoterapie   genetika   MeSH
• ultrasonografie prenatální MeSH
• Check Tag
• kojenec MeSH
• lidé MeSH
• ženské pohlaví MeSH
• Publikační typ
• časopisecké články MeSH
• kazuistiky MeSH
• práce podpořená grantem MeSH
• Názvy látek
• intracelulární signální peptidy a proteiny MeSH
• lidský růstový hormon MeSH
• SHOC2 protein, human MeSH Prohlížeč