INTRODUCTION: Keratoconus is a relatively frequent disease leading to severe visual impairment. Existing therapies are imperfect and clinical management may benefit from improved understanding of mechanisms leading to this disease. We aim to investigate the replication of 11 single nucleotide polymorphisms (SNPs) with keratoconus. METHODS: SNPs from loci previously found in association with keratoconus were genotyped in 165 keratoconus cases of Caucasian Czech origin (108 males and 57 females) and 193 population and gender-matched controls. They included rs1536482 (COL5A1), rs4839200 (KCND3), rs757219 and rs214884 (IMMP2L), rs1328083 and rs1328089 (DAOA), rs2721051 (FOXO1), rs4894535 (FNDC3B), rs4954218 (MAP3K19, RAB3GAP1), rs9938149 (ZNF469) and rs1324183 (MPDZ). A case-control association analysis was assessed using Fisher's exact tests. RESULTS: The strongest association was found for rs1324183 (allelic test OR = 1.58; 95% CI, 1.10-2.24, p = 0.01). Statistically significant values were also obtained for rs2721051 (allelic test OR = 1.72; 95% CI, 1.07-2.77, p = 0.025) and rs4954218 (allelic test OR = 1.53; 95% CI, 1.01-2.34; p = 0.047) which showed an opposite effect direction compared to previously reported one. CONCLUSION: Independent replication of association between two SNPs and keratoconus supports the association of these loci with the risks for the disease development, while the effect of rs4954218 warrants further investigation. Understanding the role of the genetic factors involved in keratoconus etiopathogenesis may facilitate development of novel therapies and an early detection.

• MeSH
• celogenomová asociační studie MeSH
• dospělí MeSH
• genetická predispozice k nemoci MeSH
• genetické lokusy MeSH
• genotyp MeSH
• jednonukleotidový polymorfismus genetika   MeSH
• keratokonus epidemiologie   genetika   MeSH
• lidé středního věku MeSH
• lidé MeSH
• mladý dospělý MeSH
• replikace DNA * MeSH
• senioři nad 80 let MeSH
• senioři MeSH
• studie případů a kontrol MeSH
• Check Tag
• dospělí MeSH
• lidé středního věku MeSH
• lidé MeSH
• mladý dospělý MeSH
• mužské pohlaví MeSH
• senioři nad 80 let MeSH
• senioři MeSH
• ženské pohlaví MeSH
• Publikační typ
• časopisecké články MeSH
• srovnávací studie MeSH
• Geografické názvy
• Česká republika epidemiologie   MeSH

We observed bilateral cataracts on second trimester ultrasound, in two consecutive pregnancies, with no other structural defects detected. The parents were unrelated and had no family history for the disease. The first pregnancy was terminated in week 22. Copy number variation analysis revealed, in both the aborted fetus and the mother, a 495 kb duplication at 22q11.23 encompassing CRYBB3 and CRYBB2, and not present in variation databases. In the second pregnancy, lens hyperechogenicity was detected by ultrasound at week 13 and 4 days. The identical duplication at 22q11.23 was found in the fetus and considered as possibly pathogenic. At weeks 22 and 30, smaller orbit measurements were elucidated on ultrasound, raising concerns as to the underlying molecular genetic cause, necessitating further investigation. Whole-exome sequencing, using DNA of the first fetus, was performed shortly after the birth of a male child, and two truncating RAB3GAP1 mutations were detected: c.538G>T; p. (Glu180*) and c.943C>T; p. (Arg315*). Neither mutation has been previously reported to be disease-causing; however, evaluation in the context of previously published literature indicated their deleterious nature, implying a clinical diagnosis of Warburg micro syndrome or Martsolf syndrome. Sanger sequencing confirmed segregation of the two mutations within the family, consistent with autosomal recessive inheritance. The child born from the second pregnancy showed features typical of Warburg micro syndrome, with the exception of microcephaly, at age 31 months. © 2016 Wiley Periodicals, Inc.

• MeSH
• atrofie optického nervu diagnóza   genetika   patofyziologie   MeSH
• beta-krystaliny - řetězec B genetika   MeSH
• exony genetika   MeSH
• hypogonadismus diagnóza   genetika   patofyziologie   MeSH
• katarakta vrozené   diagnóza   genetika   patofyziologie   MeSH
• kojenec MeSH
• lidé MeSH
• mentální retardace diagnóza   genetika   patofyziologie   MeSH
• mikrocefalie diagnóza   genetika   patofyziologie   MeSH
• mnohočetné abnormality diagnóza   genetika   patofyziologie   MeSH
• mutace MeSH
• novorozenec MeSH
• potracený plod patofyziologie   MeSH
• rab3 proteiny vázající GTP genetika   MeSH
• rodokmen MeSH
• rohovka abnormality   patofyziologie   MeSH
• sekvenční analýza DNA MeSH
• těhotenství MeSH
• ultrasonografie prenatální MeSH
• variabilita počtu kopií segmentů DNA genetika   MeSH
• Check Tag
• kojenec MeSH
• lidé MeSH
• mužské pohlaví MeSH
• novorozenec MeSH
• těhotenství MeSH
• ženské pohlaví MeSH
• Publikační typ
• časopisecké články MeSH

Genome-wide studies of African populations have the potential to reveal powerful insights into the evolution of our species, as these diverse populations have been exposed to intense selective pressures imposed by infectious diseases, diet, and environmental factors. Within Africa, the Sahel Belt extensively overlaps the geographical center of several endemic infections such as malaria, trypanosomiasis, meningitis, and hemorrhagic fevers. We screened 2.5 million single nucleotide polymorphisms in 161 individuals from 13 Sahelian populations, which together with published data cover Western, Central, and Eastern Sahel, and include both nomadic and sedentary groups. We confirmed the role of this Belt as a main corridor for human migrations across the continent. Strong admixture was observed in both Central and Eastern Sahelian populations, with North Africans and Near Eastern/Arabians, respectively, but it was inexistent in Western Sahelian populations. Genome-wide local ancestry inference in admixed Sahelian populations revealed several candidate regions that were significantly enriched for non-autochthonous haplotypes, and many showed to be under positive selection. The DARC gene region in Arabs and Nubians was enriched for African ancestry, whereas the RAB3GAP1/LCT/MCM6 region in Oromo, the TAS2R gene family in Fulani, and the ALMS1/NAT8 in Turkana and Samburu were enriched for non-African ancestry. Signals of positive selection varied in terms of geographic amplitude. Some genomic regions were selected across the Belt, the most striking example being the malaria-related DARC gene. Others were Western-specific (oxytocin, calcium, and heart pathways), Eastern-specific (lipid pathways), or even population-restricted (TAS2R genes in Fulani, which may reflect sexual selection).

• MeSH
• acetyltransferasy genetika   MeSH
• genom lidský * MeSH
• haplotypy MeSH
• hemoragické horečky virové genetika   MeSH
• jednonukleotidový polymorfismus MeSH
• krevní skupiny - systém Duffy genetika   MeSH
• lidé MeSH
• malárie genetika   MeSH
• MCM komplex, komponenta 6 genetika   MeSH
• meningitida genetika   MeSH
• migrace lidstva * MeSH
• proteiny genetika   MeSH
• receptory buněčného povrchu genetika   MeSH
• receptory spřažené s G-proteiny genetika   MeSH
• selekce (genetika) * MeSH
• Check Tag
• lidé MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH
• Geografické názvy
• Afrika MeSH