AIM: To study congenital heart defects (CHDs), evaluate their relation to extra-cardiac pathologies, and assess the significance of prenatal diagnostics for heart diseases. METHODS: Data from 1999-2017 were analyzed for the incidence of significant CHDs in fetuses (prenatal ultrasound/echocardiography) and children, including, where applicable, autopsy data and genetic evaluation. RESULTS: Among 220,400 fetuses, 819 (3.7 cases per 1000) significant CHDs were observed. Of the total, 53% (435/819) of CHDs were diagnosed prenatally. The heart defect was an isolated impairment in 78% (640/819), associated with a genetic impairment in 16% (128/819), and with extra-cardiac malformations without genetic pathology in 6% (51/819). Chromosomal aberrations were diagnosed prenatally in 70% (90/128) of those affected and extra-cardiac conditions in 86% (44/51). The CHD and genetic pathology association was more frequent prenatally [21% (90/435) vs. postnatally: 10% (38/384; P<0.0001)], as was the association between CHD with other extra-cardiac pathology and a normal karyotype [prenatally: 10% (44/435) vs. postnatally: 2% (7/384; P<0.0001)]. CONCLUSION: Heart defects are most frequently isolated, with genetic and other extra-cardiac anomalies in about one third of cases, significantly linked to prenatal diagnostics.

• Klíčová slova
• aneuploidy, congenital heart defect, extracardiac malformation, fetal echocardiography, genetic abnormality, screening,
• MeSH
• chromozomální aberace embryologie   MeSH
• echokardiografie MeSH
• gestační stáří MeSH
• incidence MeSH
• lidé MeSH
• novorozenec MeSH
• pitva MeSH
• prenatální diagnóza * statistika a číselné údaje   MeSH
• retrospektivní studie MeSH
• těhotenství MeSH
• ultrasonografie prenatální MeSH
• vrozené srdeční vady diagnostické zobrazování   embryologie   mortalita   MeSH
• výsledek těhotenství MeSH
• Check Tag
• lidé MeSH
• novorozenec MeSH
• těhotenství MeSH
• ženské pohlaví MeSH
• Publikační typ
• časopisecké články MeSH

Disorders of ATP synthase, the key enzyme of mitochondrial energy provision belong to the most severe metabolic diseases presenting as early-onset mitochondrial encephalo-cardiomyopathies. Up to now, mutations in four nuclear genes were associated with isolated deficiency of ATP synthase. Two of them, ATP5A1 and ATP5E encode enzyme's structural subunits alpha and epsilon, respectively, while the other two ATPAF2 and TMEM70 encode specific ancillary factors that facilitate the biogenesis of ATP synthase. All these defects share a similar biochemical phenotype with pronounced decrease in the content of fully assembled and functional ATP synthase complex. However, substantial differences can be found in their frequency, molecular mechanism of pathogenesis, clinical manifestation as well as the course of the disease progression. While for TMEM70 the number of reported patients as well as spectrum of the mutations is steadily increasing, mutations in ATP5A1, ATP5E and ATPAF2 genes are very rare. Apparently, TMEM70 gene is highly prone to mutagenesis and this type of a rare mitochondrial disease has a rather frequent incidence. Here we present overview of individual reported cases of nuclear mutations in ATP synthase and discuss, how their analysis can improve our understanding of the enzyme biogenesis.

• MeSH
• genetická predispozice k nemoci genetika   MeSH
• jednonukleotidový polymorfismus genetika   MeSH
• lidé MeSH
• mitochondriální nemoci enzymologie   genetika   MeSH
• mitochondriální protonové ATPasy genetika   MeSH
• mitochondrie enzymologie   genetika   patologie   MeSH
• modely genetické MeSH
• mutace genetika   MeSH
• zvířata MeSH
• Check Tag
• lidé MeSH
• zvířata MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH
• přehledy MeSH
• Názvy látek
• mitochondriální protonové ATPasy MeSH

Objectives: This study aimed to evaluate the prenatal rate of congenital heart defects (CHDs) and the frequency of termination of pregnancy (TOP) due to a CHD, depending on the severity of the defect and concomitant diseases of the fetus.Methods: The data were assessed retrospectively between 2002 and 2017. Ultrasound examination was performed mostly in the second trimester. For analysis, the CHDs were divided into three groups of severity and three groups of fetus impairment.Results: A total of 40,885 fetuses underwent echocardiography. The CHDs were detected in 1.0% (398/40,885) and were an isolated anomaly in 69% (275/398). Forty-nine percent (197/398) of families decided to TOP. In all groups of severity, the rate of TOP rose linearly when comparing isolated defects and cases with associated morphological and genetic impairments. The TOP was significantly dependent on the associated anomalies in patients with the most correctable defects (p < .001) and the severity of CHDs in isolated cases without any other impairment (p < .001).Conclusion: The parents' decision to terminate increased with the severity of the defect and the associated anomalies of the fetus. The parents were mostly influenced by the associated anomalies when the CHD was correctable, and genetic factors played a more important role than morphological ones.

• Klíčová slova
• Congenital heart defect, fetal echocardiography, screening, termination of pregnancy,
• MeSH
• echokardiografie MeSH
• lidé MeSH
• plod MeSH
• retrospektivní studie MeSH
• rodiče MeSH
• těhotenství MeSH
• ultrasonografie prenatální MeSH
• vrozené srdeční vady * diagnostické zobrazování   epidemiologie   MeSH
• Check Tag
• lidé MeSH
• těhotenství MeSH
• ženské pohlaví MeSH
• Publikační typ
• časopisecké články MeSH

The present paper illustrates the author's 25-year experience in a step by step approach to the definition of environmental and genetic background of neural tube defects. Based on the birth defects registry, a complete ascertainment of all deliveries was performed in Southern Poland during two periods: 1970-1972, and 1979-1981. The birth prevalence of neural tube defects (NTD), as well as other CNS malformations was determined. The empiric recurrence risk was calculated as 3.2% +/- 1.6. Based on this figure, the relative risk (RR = 37.6 p < 0.001) and heritability (h2 = 74.7 +/- 6.7) were estimated. Our own modification of Morton's complex segregation analysis was applied. Three Mendelian (dominant, additive and recessive) and one multifactorial model were tested. The results did not provide a clear cut discrimination between different models; however the lowest x2 value was obtained for additive inheritance with 61% of penetrance and the frequency of sporadic cases equaled 55%. A search for genetic markers did not support the hypothesis that HLA-A,B,C loci are equivalents of T/t like locus in mice. The results of the study on transcobalamine levels in amniotic fluid may suggests that different transcobalamine metabolism reflects phenotypic expression of genetic susceptibility to NTD development. Current research status and future perspectives on genetic and environmental background of NTD are also presented.

• MeSH
• abnormality vyvolané léky epidemiologie   MeSH
• defekty neurální trubice epidemiologie   genetika   MeSH
• genetické markery MeSH
• lidé MeSH
• modely genetické MeSH
• modely nemocí na zvířatech MeSH
• myši MeSH
• novorozenec MeSH
• pravděpodobnostní funkce MeSH
• registrace MeSH
• těhotenství MeSH
• zvířata MeSH
• Check Tag
• lidé MeSH
• mužské pohlaví MeSH
• myši MeSH
• novorozenec MeSH
• těhotenství MeSH
• ženské pohlaví MeSH
• zvířata MeSH
• Publikační typ
• časopisecké články MeSH
• přehledy MeSH
• Geografické názvy
• Polsko epidemiologie   MeSH
• Názvy látek
• genetické markery MeSH

• MeSH
• genetická vazba MeSH
• hlavní histokompatibilní komplex * MeSH
• krysa rodu Rattus MeSH
• rozmnožování * MeSH
• tělesná hmotnost * MeSH
• zvířata MeSH
• Check Tag
• krysa rodu Rattus MeSH
• mužské pohlaví MeSH
• ženské pohlaví MeSH
• zvířata MeSH
• Publikační typ
• časopisecké články MeSH
• Research Support, U.S. Gov't, P.H.S. MeSH

AIMS: The aim of this retrospective study was to determine the detection rate of the pathogenic copy number variants (CNVs) in a cohort of 33 foetuses - 32 with CHD (congenital heart defects) and 1 with kidney defect, after exclusion of common aneuploidies (trisomy 13, 18, 21, and monosomy X) by karyotyping, Multiplex ligation - dependent probe amplification (MLPA) and chromosomal microarray analysis (CMA). We also assess the effectivity of MLPA as a method of the first tier for quick and inexpensive detection of mutations, causing congenital malformations in foetuses. METHODS: MLPA with probe mixes P070, P036 - Telomere 3 and 5, P245 - microdeletions, P250 - DiGeorge syndrome, and P311 - CHD (Congenital heart defects) was performed in 33 samples of amniotic fluid and chorionic villi. CMA was performed in 10 relevant cases. RESULTS: Pathogenic CNVs were found in 5 samples: microdeletions in region 22q11.2 (≈2 Mb) in two foetuses, one distal microdeletion of the 22q11.2 region containing genes LZTR1, CRKL, AIFM3 and SNAP29 (≈416 kb) in the foetus with bilateral renal agenesis, 8p23.1 (3.8 Mb) microdeletion syndrome and microdeletion in area 9q34.3 (1.7 Mb, Kleefstra syndrome). MLPA as an initial screening method revealed unambiguously pathogenic CNVs in 15.2 % of samples. CONCLUSION: Our study suggests that MLPA and CMA are a reliable and high-resolution technology and should be used as the first-tier test for prenatal diagnosis of congenital heart disease. Determination of the cause of the abnormality is crucial for genetic counselling and further management of the pregnancy.

• Klíčová slova
• bilateral renal agenesis, clinical variability, congenital heart defect, copy number variants,
• MeSH
• lidé MeSH
• pilotní projekty MeSH
• plod MeSH
• retrospektivní studie MeSH
• těhotenství MeSH
• transkripční faktory genetika   MeSH
• variabilita počtu kopií segmentů DNA * genetika   MeSH
• vrozené srdeční vady * diagnóza   genetika   MeSH
• Check Tag
• lidé MeSH
• těhotenství MeSH
• ženské pohlaví MeSH
• Publikační typ
• časopisecké články MeSH
• Názvy látek
• LZTR1 protein, human MeSH Prohlížeč
• transkripční faktory MeSH

Although awareness of familial hypercholesterolemia (FH) is increasing, this common, potentially fatal, treatable condition remains underdiagnosed. Despite FH being a genetic disorder, genetic testing is rarely used. The Familial Hypercholesterolemia Foundation convened an international expert panel to assess the utility of FH genetic testing. The rationale includes the following: 1) facilitation of definitive diagnosis; 2) pathogenic variants indicate higher cardiovascular risk, which indicates the potential need for more aggressive lipid lowering; 3) increase in initiation of and adherence to therapy; and 4) cascade testing of at-risk relatives. The Expert Consensus Panel recommends that FH genetic testing become the standard of care for patients with definite or probable FH, as well as for their at-risk relatives. Testing should include the genes encoding the low-density lipoprotein receptor (LDLR), apolipoprotein B (APOB), and proprotein convertase subtilisin/kexin 9 (PCSK9); other genes may also need to be considered for analysis based on patient phenotype. Expected outcomes include greater diagnoses, more effective cascade testing, initiation of therapies at earlier ages, and more accurate risk stratification.

• Klíčová slova
• cascade testing, consensus statement, familial hypercholesterolemia, genetic counseling, genetic testing,
• MeSH
• apolipoproteiny B krev   genetika   MeSH
• genetické poradenství metody   normy   MeSH
• genetické testování metody   normy   MeSH
• hyperlipoproteinemie typ II krev   diagnóza   genetika   MeSH
• lidé MeSH
• proproteinkonvertasa subtilisin/kexin typu 9 krev   genetika   MeSH
• receptory LDL krev   genetika   MeSH
• Check Tag
• lidé MeSH
• Publikační typ
• časopisecké články MeSH
• přehledy MeSH
• Názvy látek
• apolipoproteiny B MeSH
• LDLR protein, human MeSH Prohlížeč
• PCSK9 protein, human MeSH Prohlížeč
• proproteinkonvertasa subtilisin/kexin typu 9 MeSH
• receptory LDL MeSH

INTRODUCTION: Achromatopsia is an autosomal recessive retinal disorder with an estimated prevalence ranging from 1 in 30.000 to 50.000. The disease is caused by mutations in six different genes. The aim of the study was to perform molecular genetic analysis in 11 unrelated probands with a clinical diagnosis of achromatopsia and to describe clinical findings in those that were found to carry biallelic pathogenic mutations. METHODS: All probands and their parents underwent ophthalmic examination. Mutation detection was performed using Sanger sequencing of CNGB3 exons 6, 7, 9-13, which have been found to harbour most disease-causing mutations in patients with achromatopsia of European origin. RESULTS: Three known pathogenic variants in CNGB3 were identified in 2 probands. Proband 1 was a compound heterozygote for the c.819_826del; p.(Arg274Valfs*13) and c.1006G>T; p.(Glu336*). Proband 2 carried the c.1148del; p.(Thr383Ilefs*13) in a homozygous state. The best corrected visual acuity in proband 1 (aged 19 years) was 0.1 in both eyes, in proband 2 (aged 8 years) 0.05 in the right eye and 0.1 in the left eye. Both individuals had nystagmus, photophobia, and absence of colour discrimination. Fundus examination appeared normal however spectral-domain optical coherence tomography revealed subtle bilaterally symmetrical structural changes in the fovea. CONCLUSION: Molecular genetic analysis of Czech patients with achromatopsia was performed for the first time. Identification of disease-causing mutations in achromatopsia is important for establishing an early diagnosis, participation in clinical trials assessing gene therapies and may be also used for preimplantation genetic diagnosis.

• Klíčová slova
• CNGB3, achromatopsia, the Czech population,
• MeSH
• dítě MeSH
• kationtové kanály řízené cyklickými nukleotidy genetika   MeSH
• lidé MeSH
• mladý dospělý MeSH
• mutace MeSH
• mutační analýza DNA MeSH
• optická koherentní tomografie MeSH
• poruchy barevného vidění genetika   MeSH
• rodokmen MeSH
• Check Tag
• dítě MeSH
• lidé MeSH
• mladý dospělý MeSH
• Publikační typ
• časopisecké články MeSH
• Geografické názvy
• Česká republika MeSH
• Názvy látek
• CNGB3 protein, human MeSH Prohlížeč
• kationtové kanály řízené cyklickými nukleotidy MeSH

INTRODUCTION AND OBJECTIVES: Limited information is available on the safety of pregnancy in patients with genetic dilated cardiomyopathy (DCM) and in carriers of DCM-causing genetic variants without the DCM phenotype. We assessed cardiac, obstetric, and fetal or neonatal outcomes in this group of patients. METHODS: We studied 48 women carrying pathogenic or likely pathogenic DCM-associated variants (30 with DCM and 18 without DCM) who had 83 pregnancies. Adverse cardiac events were defined as heart failure (HF), sustained ventricular tachycardia, ventricular assist device implantation, heart transplant, and/or maternal cardiac death during pregnancy, or labor and delivery, and up to the sixth postpartum month. RESULTS: A total of 15 patients, all with DCM (31% of the total cohort and 50% of women with DCM) experienced adverse cardiac events. Obstetric and fetal or neonatal complications were observed in 14% of pregnancies (10 in DCM patients and 2 in genetic carriers). We analyzed the 30 women who had been evaluated before their first pregnancy (12 with overt DCM and 18 without the phenotype). Five of the 12 (42%) women with DCM had adverse cardiac events despite showing NYHA class I or II before pregnancy. Most of these women had a history of cardiac events before pregnancy (80%). Among the 18 women without phenotype, 3 (17%) developed DCM toward the end of pregnancy. CONCLUSIONS: Cardiac complications during pregnancy and postpartum were common in patients with genetic DCM and were primarily related to HF. Despite apparently good tolerance of pregnancy in unaffected genetic carriers, pregnancy may act as a trigger for DCM onset in a subset of these women.

• Klíčová slova
• Dilated cardiomyopathy, Embarazo, Heart failure, Insuficiencia cardiaca, Miocardiopatía dilatada, Mutation, Pregnancy, Variante genética,
• MeSH
• dilatační kardiomyopatie * genetika   komplikace   MeSH
• dospělí MeSH
• fenotyp MeSH
• genetická variace MeSH
• kardiovaskulární komplikace v těhotenství * genetika   MeSH
• lidé MeSH
• těhotenství MeSH
• výsledek těhotenství * MeSH
• Check Tag
• dospělí MeSH
• lidé MeSH
• těhotenství MeSH
• ženské pohlaví MeSH
• Publikační typ
• časopisecké články MeSH

• MeSH
• alfa-fetoproteiny analýza   MeSH
• analýza určování pohlaví MeSH
• defekty neurální trubice diagnóza   MeSH
• genetické nemoci vrozené diagnóza   prevence a kontrola   MeSH
• genetické poradenství * MeSH
• lidé MeSH
• plodová voda analýza   MeSH
• prenatální diagnóza metody   MeSH
• radioimunoanalýza MeSH
• těhotenství MeSH
• testosteron analýza   MeSH
• vrozené poruchy metabolismu diagnóza   MeSH
• Check Tag
• lidé MeSH
• mužské pohlaví MeSH
• těhotenství MeSH
• ženské pohlaví MeSH
• Publikační typ
• časopisecké články MeSH
• Názvy látek
• alfa-fetoproteiny MeSH
• testosteron MeSH