BACKGROUND: Mutations in FOXL2 are known to cause autosomal dominant blepharophimosis-ptosis-epicanthus inversus syndrome (BPES), variably associated with premature ovarian failure. In this study, we report results of mutational screening in a Czech and Slovak patient population with BPES. DESIGN: Case series. PARTICIPANTS: Thirteen probands of Czech and one proband of Slovak origin with BPES and their available family members. METHODS: Sanger sequencing and multiplex ligation-dependent probe amplification in 14 probands with BPES. Targeted mutational screening in first-degree relatives. MAIN OUTCOME MEASURES: Genetic characterization and phenotype evaluation in Czech and Slovak individuals with BPES and their family members. RESULTS: Eight different mutations were detected including three novel ones: c.5T>G; p.(Met2Arg), c.197C>A; p.(Ala66Glu) and c.701_702insTGCAGCCGCAGCGGCTGCAGCAGCTGCGGCTGCAGCCGC; p.(Ala222_Ala234dup). In one family, the molecular genetic cause of disease was not identified by the methodology used. In 13 pedigrees, a negative family history suggested a de novo origin, which could be confirmed by targeted mutational screening in four families. One 62-year-old female with the c.663_692dup30 mutation had an atypical phenotype presenting as moderate ptosis compensated by frontalis muscle contraction, no epicanthus inversus and no premature ovarian failure. CONCLUSIONS: The de novo mutation rate in FOXL2 is exceptionally high compared with other dominant disorders manifesting with an ocular phenotype. In cases reporting a negative family history, careful examination of both parents is important to exclude mild features of the BPES phenotype.

• MeSH
• blefarofimóza genetika   MeSH
• dítě MeSH
• DNA sondy MeSH
• dospělí MeSH
• fenotyp MeSH
• forkhead transkripční faktory genetika   MeSH
• genetické asociační studie MeSH
• kojenec MeSH
• kožní abnormality genetika   MeSH
• lidé středního věku MeSH
• lidé MeSH
• missense mutace * MeSH
• mladiství MeSH
• multiplexová polymerázová řetězová reakce MeSH
• mutační analýza DNA MeSH
• předškolní dítě MeSH
• urogenitální abnormality genetika   MeSH
• Check Tag
• dítě MeSH
• dospělí MeSH
• kojenec MeSH
• lidé středního věku MeSH
• lidé MeSH
• mladiství MeSH
• mužské pohlaví MeSH
• předškolní dítě MeSH
• ženské pohlaví MeSH
• Publikační typ
• časopisecké články MeSH

Genitopatellar syndrome (GPS) and Say-Barber-Biesecker-Young-Simpson syndrome (SBBYSS) are two distinct clinically overlapping syndromes caused by de novo heterozygous truncating mutations in the KAT6B gene encoding lysine acetyltransferase 6B, a part of the histone H3 acetyltransferase complex. We describe an 8-year-old girl with a KAT6B mutation and a combined GPS/SBBYSS phenotype. The comparison of this patient with 61 previously published cases with KAT6B mutations and GPS, SBBYSS or combined GPS/SBBYSS phenotypes allowed us to separate the KAT6B mutations into four groups according to their position in the gene (reflecting nonsense mediated RNA decay and protein domains) and their clinical outcome. We suggest that mutations in mid-exon 18 corresponding to the C-terminal end of the acidic (Asp/Glu-rich) domain of KAT6B may have more variable expressivity leading to GPS, SBBYSS or combined phenotypes, in contrast to defects in other regions of the gene which contribute more specifically to either GPS or SBBYSS. Notwithstanding the clinical overlap, our cluster analysis of phenotypes of all known patients with KAT6B mutations supports the existence of two clinical entities, GPS and SBBYSS, as poles within the KAT6B-related disease spectrum. The awareness of these phenomena is important for qualified genetic counselling of patients with KAT6B mutations.

• MeSH
• blefarofimóza diagnóza   genetika   MeSH
• dítě MeSH
• exony * MeSH
• faciální stigmatizace MeSH
• fenotyp MeSH
• histonacetyltransferasy genetika   MeSH
• kongenitální hypotyreóza diagnóza   genetika   MeSH
• kraniofaciální abnormality diagnóza   genetika   MeSH
• ledviny abnormality   MeSH
• lidé MeSH
• mentální retardace diagnóza   genetika   MeSH
• molekulární sekvence - údaje MeSH
• mutace * MeSH
• nestabilita kloubu diagnóza   genetika   MeSH
• patela abnormality   MeSH
• psychomotorické poruchy diagnóza   genetika   MeSH
• sekvence nukleotidů MeSH
• skrotum abnormality   MeSH
• urogenitální abnormality diagnóza   genetika   MeSH
• vrozené srdeční vady diagnóza   genetika   MeSH
• Check Tag
• dítě MeSH
• lidé MeSH
• ženské pohlaví MeSH
• Publikační typ
• časopisecké články MeSH
• kazuistiky MeSH
• práce podpořená grantem MeSH