Dagmar Wieczorek

Publications (2)46.14 Total impact

• Source

  Available from: Alejandro Sifrim

  Article: Heterozygous missense mutations in SMARCA2 cause Nicolaides-Baraitser syndrome.

  Jeroen K J Van Houdt, Beata Anna Nowakowska, Sérgio B Sousa, Barbera D C van Schaik, Eve Seuntjens, Nelson Avonce, Alejandro Sifrim, Omar A Abdul-Rahman, Marie-José H van den Boogaard, Armand Bottani, [......], Catheline Vilain, Annick Vogels, Emma Wakeling, Dagmar Wieczorek, Louise Wilson, Orsetta Zuffardi, Antoine H C van Kampen, Koenraad Devriendt, Raoul Hennekam, Joris Robert Vermeesch
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  ABSTRACT: Nicolaides-Baraitser syndrome (NBS) is characterized by sparse hair, distinctive facial morphology, distal-limb anomalies and intellectual disability. We sequenced the exomes of ten individuals with NBS and identified heterozygous variants in SMARCA2 in eight of them. Extended molecular screening identified nonsynonymous SMARCA2 mutations in 36 of 44 individuals with NBS; these mutations were confirmed to be de novo when parental samples were available. SMARCA2 encodes the core catalytic unit of the SWI/SNF ATP-dependent chromatin remodeling complex that is involved in the regulation of gene transcription. The mutations cluster within sequences that encode ultra-conserved motifs in the catalytic ATPase region of the protein. These alterations likely do not impair SWI/SNF complex assembly but may be associated with disrupted ATPase activity. The identification of SMARCA2 mutations in humans provides insight into the function of the Snf2 helicase family.
  Nature Genetics 02/2012; 44(4):445-9, S1. · 35.53 Impact Factor
• Source

  Available from: Caio Robledo D C Quaio

  Article: Mutations in SRCAP, encoding SNF2-related CREBBP activator protein, cause Floating-Harbor syndrome.

  Rebecca L Hood, Matthew A Lines, Sarah M Nikkel, Jeremy Schwartzentruber, Chandree Beaulieu, Małgorzata J M Nowaczyk, Judith Allanson, Chong Ae Kim, Dagmar Wieczorek, Jukka S Moilanen, [......], George McGillivray, Ruobing Zou, D Ross McLeod, Albert E Chudley, Bernard N Chodirker, Janet Marcadier, Jacek Majewski, Dennis E Bulman, Susan M White, Kym M Boycott
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  ABSTRACT: Floating-Harbor syndrome (FHS) is a rare condition characterized by short stature, delayed osseous maturation, expressive-language deficits, and a distinctive facial appearance. Occurrence is generally sporadic, although parent-to-child transmission has been reported on occasion. Employing whole-exome sequencing, we identified heterozygous truncating mutations in SRCAP in five unrelated individuals with sporadic FHS. Sanger sequencing identified mutations in SRCAP in eight more affected persons. Mutations were de novo in all six instances in which parental DNA was available. SRCAP is an SNF2-related chromatin-remodeling factor that serves as a coactivator for CREB-binding protein (CREBBP, better known as CBP, the major cause of Rubinstein-Taybi syndrome [RTS]). Five SRCAP mutations, two of which are recurrent, were identified; all are tightly clustered within a small (111 codon) region of the final exon. These mutations are predicted to abolish three C-terminal AT-hook DNA-binding motifs while leaving the CBP-binding and ATPase domains intact. Our findings show that SRCAP mutations are the major cause of FHS and offer an explanation for the clinical overlap between FHS and RTS.
  The American Journal of Human Genetics 02/2012; 90(2):308-13. · 10.60 Impact Factor