Heterozygous missense mutations in SMARCA2 cause Nicolaides-Baraitser syndrome

JKJ Van Houdt, BA Nowakowska, SB Sousa, BDC van Schaik, E Seuntjens, N Avonce, A Sifrim, OA Abdul-Rahman, MJH van den Boogaard, A Bottani, M Castori, V Cormier-Daire, MA Deardorff, I Filges, A Fryer, JP Fryns, S Gana, L Garavelli, G Gillessen-Kaesbach, BD HallD Horn, Danny Huylebroeck, J Klapecki, M Krajewska-Walasek, A Kuechler, MA Lines, S Maas, KD MacDermot, S Mckee, A Magee, Stella Man, Y Moreau, F Morice-Picard, E Obersztyn, J Pilch, E Rosser, N Shannon, I Stolte-Dijkstra, P Van Dijck, C Vilain, Alain Vogels, E Wakeling, D Wieczorek, L Wilson, O Zuffardi, AHC van Kampen, K DeVriendt, R Hennekam, JR Vermeesch

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173 Citations (Scopus)

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.
Original languageUndefined/Unknown
Pages (from-to)445-U261
JournalNature Genetics
Volume44
Issue number4
DOIs
Publication statusPublished - 2012

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