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

BACKGROUND: Presence of multiple cardiac rhabdomyomas is one of the major features of Tuberous sclerosis (TSC), but isolated progressing single giant rhabdomyoma is very rare and not typical of TSC. CASE REPORT: This report presents family without obvious history of TSC with occurrence of giant mediastinal rhabdomyoma affecting the haemodynamics in male foetus, without other TSC symptoms. Girl from the next gravidity had prenatally detected multiple rhabdomyomas and small subcortical tuber of brain detected after birth. DNA analysis found novel c.4861A>T TSC2 variant and large deletion in TSC2 in tumour tissue from male foetus. The novel TSC2 variant was also present in the girl and her healthy father, in silico analysis suggested its functional effect on TSC2. Brain MRI of the father detected mild TSC specific abnormality. CONCLUSION: We suggest the novel TSC2 mutation is a cause of mild TSC in this family and has reduced expression. The clinical and molecular findings in this family also emphasize that TSC diagnosis should be also evaluated in case of single giant foetal cardiac rhabdomyoma.

• Klíčová slova
• TSC2, cardiac rhabdomyoma, mild tuberous sclerosis., reduced expression,
• MeSH
• genetická predispozice k nemoci MeSH
• genetické testování MeSH
• hamartin MeSH
• indukovaný potrat MeSH
• lidé MeSH
• mutační analýza DNA MeSH
• nádorové supresorové proteiny genetika   MeSH
• nádory mediastina komplikace   diagnóza   genetika   MeSH
• nemoci plodu diagnóza   genetika   MeSH
• novorozenec MeSH
• pitva MeSH
• prediktivní hodnota testů MeSH
• prenatální diagnóza MeSH
• rhabdomyom komplikace   diagnóza   genetika   MeSH
• těhotenství MeSH
• tuberin MeSH
• tuberózní skleróza komplikace   diagnóza   genetika   MeSH
• vzácné nemoci diagnóza   genetika   MeSH
• Check Tag
• lidé MeSH
• mužské pohlaví MeSH
• novorozenec MeSH
• těhotenství MeSH
• ženské pohlaví MeSH
• Publikační typ
• časopisecké články MeSH
• kazuistiky MeSH
• Názvy látek
• hamartin MeSH
• nádorové supresorové proteiny MeSH
• TSC2 protein, human MeSH Prohlížeč
• tuberin MeSH