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.

• Klíčová slova
• CRYBB2, CRYBB3, DNA copy number variations, RAB3GAP1, Warburg micro syndrome, high-throughput nucleotide sequencing, prenatal ultrasonography,
• 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
• práce podpořená grantem MeSH
• Názvy látek
• beta-crystallin B2 MeSH Prohlížeč
• beta-krystaliny - řetězec B MeSH
• CRYBB3 protein, human MeSH Prohlížeč
• Rab3 proteiny vázající GTP MeSH
• RAB3GAP1 protein, human MeSH Prohlížeč