TY - JOUR
T1 - The spectrum of DNMT3A variants in Tatton–Brown–Rahman syndrome overlaps with that in hematologic malignancies
AU - Shen, Wei
AU - Heeley, Jennifer M.
AU - Carlston, Colleen M.
AU - Acuna-Hidalgo, Rocio
AU - Nillesen, Willy M.
AU - Dent, Karin M.
AU - Douglas, Ganka V.
AU - Levine, Kara L.
AU - Bayrak-Toydemir, Pinar
AU - Marcelis, Carlo L.
AU - Shinawi, Marwan
AU - Carey, John C.
N1 - Publisher Copyright:
© 2017 Wiley Periodicals, Inc.
PY - 2017/11
Y1 - 2017/11
N2 - De novo, germline variants in DNMT3A cause Tatton–Brown–Rahman syndrome (TBRS). This condition is characterized by overgrowth, distinctive facial appearance, and intellectual disability. Somatic DNMT3A variants frequently occur in hematologic malignances, particularly acute myeloid leukemia. The Arg882 residue is the most common site of somatic DNMT3A variants, and has also been altered in patients with TBRS. Here we present three additional patients with this disorder attributed to DNMT3A germline variants that disrupt the Arg882 codon, suggesting that this codon may be a germline mutation hotspot in this disorder. Furthermore, based on the investigation of previously reported variants in patients with TBRS, we found overlap in the spectrum of DNMT3A variants observed in this disorder and somatic variants in hematological malignancies.
AB - De novo, germline variants in DNMT3A cause Tatton–Brown–Rahman syndrome (TBRS). This condition is characterized by overgrowth, distinctive facial appearance, and intellectual disability. Somatic DNMT3A variants frequently occur in hematologic malignances, particularly acute myeloid leukemia. The Arg882 residue is the most common site of somatic DNMT3A variants, and has also been altered in patients with TBRS. Here we present three additional patients with this disorder attributed to DNMT3A germline variants that disrupt the Arg882 codon, suggesting that this codon may be a germline mutation hotspot in this disorder. Furthermore, based on the investigation of previously reported variants in patients with TBRS, we found overlap in the spectrum of DNMT3A variants observed in this disorder and somatic variants in hematological malignancies.
KW - DNMT3A
KW - Tatton–Brown–Rahman syndrome
KW - exome sequencing
KW - hematologic malignancies
UR - http://www.scopus.com/inward/record.url?scp=85031940772&partnerID=8YFLogxK
U2 - 10.1002/ajmg.a.38485
DO - 10.1002/ajmg.a.38485
M3 - Article
C2 - 28941052
AN - SCOPUS:85031940772
SN - 1552-4825
VL - 173
SP - 3022
EP - 3028
JO - American Journal of Medical Genetics, Part A
JF - American Journal of Medical Genetics, Part A
IS - 11
ER -