TY - JOUR
T1 - Genotype-phenotype correlation of coffin-siris syndrome caused by mutations in SMARCB1, SMARCA4, SMARCE1, and ARID1A
AU - Coffin-Siris Syndrome International Collaborators
AU - Kosho, Tomoki
AU - Okamoto, Nobuhiko
AU - Imai, Yoko
AU - Ohashi, Hirofumi
AU - van Eerde, Albertien M.
AU - Chrzanowska, Krystyna
AU - Clayton-Smith, Jill
AU - Kingston, Helen
AU - Mari, Francesca
AU - Aggarwal, Shagun
AU - Mowat, David
AU - Niikawa, Norio
AU - Hiraki, Yoko
AU - Matsumoto, Naoya
AU - Fukushima, Yoshimitsu
AU - Josifova, Dragana
AU - Dean, John
AU - Smigiel, Robert
AU - Sakazume, Satoru
AU - Silengo, Margherita
AU - Tinschert, Sigrid
AU - Kawame, Hiroshi
AU - Yano, Shoji
AU - Yamagata, Takanori
AU - van Bon, Bregje W.M.
AU - Vulto-van Silfhout, Anneke T.
AU - Ben-Omran, Tawfeg
AU - Bigoni, Stefania
AU - Alanay, Yasemin
AU - Miyake, Noriko
AU - Tsurusaki, Yoshinori
AU - Matsumoto, Naomichi
AU - Santen, Gijs W.E.
AU - Wieczorek, Dagmar
AU - Wollnik, Bernd
AU - Hennekam, Raul C.M.
N1 - Publisher Copyright:
© 2014 Wiley Periodicals, Inc.
PY - 2014/9
Y1 - 2014/9
N2 - Coffin-Siris syndrome (CSS) is a rare congenitalmalformation syndrome, recently found to be caused bymutations in several genes encoding components of the BAF complex. To date, 109 patients have been reported with their mutations: SMARCB1 (12%), SMARCA4 (11%), SMARCE1 (2%), ARID1A (7%), ARID1B (65%), and PHF6 (2%). We review genotype-phenotype correlation of all previously reported patients with mutations in SMARCB1, SMARCA4, SMARCE1, and ARID1A through reassessment of their clinical andmolecular findings. Cardinal features of CSS included variable degrees of intellectual disability (ID) predominantly affecting speech, sucking/feeding difficulty, and craniofacial (thick eyebrows, long eyelashes), digital (hypoplastic 5th fingers or toes, hypoplastic 5th fingernails or toenails), and other characteristics (hypertrichosis). In addition, patients withSMARCB1 mutations had severe neurodevelopmental deficits including severe ID, seizures, CNS structural abnormalities, and no expressive words as well as scoliosis. Especially, those with a recurrent mutation "p. Lys364del" represented strikingly similar phenotypes including characteristic facial coarseness. Patients with SMARCA4 mutations had less coarse craniofacial appearances and behavioral abnormalities. Patients with SMARCE1 mutations had a wide spectrum of manifestations fromsevere to moderate ID. Patients with ARID1A also had a wide spectrum of manifestations from severe ID and serous internal complications that could result in early death to mild ID. Mutations in SMARCB1, SMARCA4, and SMARCE1 are expected to exert dominant-negative or gain-of-function effects, whereas those in ARID1A are expected to exert loss-of-function effects.
AB - Coffin-Siris syndrome (CSS) is a rare congenitalmalformation syndrome, recently found to be caused bymutations in several genes encoding components of the BAF complex. To date, 109 patients have been reported with their mutations: SMARCB1 (12%), SMARCA4 (11%), SMARCE1 (2%), ARID1A (7%), ARID1B (65%), and PHF6 (2%). We review genotype-phenotype correlation of all previously reported patients with mutations in SMARCB1, SMARCA4, SMARCE1, and ARID1A through reassessment of their clinical andmolecular findings. Cardinal features of CSS included variable degrees of intellectual disability (ID) predominantly affecting speech, sucking/feeding difficulty, and craniofacial (thick eyebrows, long eyelashes), digital (hypoplastic 5th fingers or toes, hypoplastic 5th fingernails or toenails), and other characteristics (hypertrichosis). In addition, patients withSMARCB1 mutations had severe neurodevelopmental deficits including severe ID, seizures, CNS structural abnormalities, and no expressive words as well as scoliosis. Especially, those with a recurrent mutation "p. Lys364del" represented strikingly similar phenotypes including characteristic facial coarseness. Patients with SMARCA4 mutations had less coarse craniofacial appearances and behavioral abnormalities. Patients with SMARCE1 mutations had a wide spectrum of manifestations fromsevere to moderate ID. Patients with ARID1A also had a wide spectrum of manifestations from severe ID and serous internal complications that could result in early death to mild ID. Mutations in SMARCB1, SMARCA4, and SMARCE1 are expected to exert dominant-negative or gain-of-function effects, whereas those in ARID1A are expected to exert loss-of-function effects.
KW - ARID1A
KW - BAF (mSWI/SNF) complex
KW - Coffin-siris syndrome
KW - Intellectual disability (ID)
KW - SMARCA4
KW - SMARCB1
KW - SMARCE1
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UR - http://www.scopus.com/inward/citedby.url?scp=84908615607&partnerID=8YFLogxK
U2 - 10.1002/ajmg.c.31407
DO - 10.1002/ajmg.c.31407
M3 - Article
C2 - 25168959
AN - SCOPUS:84908615607
VL - 166
SP - 262
EP - 275
JO - American Journal of Medical Genetics, Part C: Seminars in Medical Genetics
JF - American Journal of Medical Genetics, Part C: Seminars in Medical Genetics
SN - 1552-4868
IS - 3
ER -