Details

Autor(en) / Beteiligte

• Lim, Elaine T
• Uddin, Mohammed
• De Rubeis, Silvia
• Chan, Yingleong
• Kamumbu, Anne S
• Zhang, Xiaochang
• D'Gama, Alissa M
• Kim, Sonia N
• Hill, Robert Sean
• Goldberg, Arthur P
• Poultney, Christopher
• Minshew, Nancy J
• Kushima, Itaru
• Aleksic, Branko
• Ozaki, Norio
• Parellada, Mara
• Arango, Celso
• Penzol, Maria J
• Carracedo, Angel
• Kolevzon, Alexander
• Hultman, Christina M
• Weiss, Lauren A
• Fromer, Menachem
• Chiocchetti, Andreas G
• Freitag, Christine M
• Church, George M
• Scherer, Stephen W
• Buxbaum, Joseph D
• Walsh, Christopher A

Titel

Rates, distribution and implications of postzygotic mosaic mutations in autism spectrum disorder

Ist Teil von

• Nature neuroscience, 2017-09, Vol.20 (9), p.1217-1224

Ort / Verlag

United States

Erscheinungsjahr

2017

Quelle

MEDLINE

Beschreibungen/Notizen

• We systematically analyzed postzygotic mutations (PZMs) in whole-exome sequences from the largest collection of trios (5,947) with autism spectrum disorder (ASD) available, including 282 unpublished trios, and performed resequencing using multiple independent technologies. We identified 7.5% of de novo mutations as PZMs, 83.3% of which were not described in previous studies. Damaging, nonsynonymous PZMs within critical exons of prenatally expressed genes were more common in ASD probands than controls (P < 1 × 10 ), and genes carrying these PZMs were enriched for expression in the amygdala (P = 5.4 × 10 ). Two genes (KLF16 and MSANTD2) were significantly enriched for PZMs genome-wide, and other PZMs involved genes (SCN2A, HNRNPU and SMARCA4) whose mutation is known to cause ASD or other neurodevelopmental disorders. PZMs constitute a significant proportion of de novo mutations and contribute importantly to ASD risk.