Coffin-Siris syndrome with café-au-lait spots, obesity and hyperinsulinism caused by a mutation in the ARID1B gene.
Coffin-Siris syndrome (CSS) (MIM 135900) is characterized by developmental delay, severe speech impairment, distinctive facial features, hypertrichosis, aplasia or hypoplasia of the distal phalanx or nail of the fifth digit and agenesis of the corpus callosum. Recently, it was shown that mutations in the ARID1B gene are the main cause of CSS, accounting for 76% of identified mutations. Here, we report a 15 year-old female patient who was admitted to our clinic with seizures, speech problems, dysmorphic features, bilaterally big, large thumb, café-au-lait (CAL) spots, obesity and hyperinsulinism. First, the patient was thought to have an association of neurofibromatosis and Rubinstein Taybi syndrome. Because of the large size of the NF1 gene for neurofibromatosis and CREBBP gene for Rubinstein Taybi syndrome, whole exome sequence analysis (WES) was conducted and a novel ARID1B mutation was identified. The proband WES test identified a novel heterozygous frameshift mutation c.3394_3395insTA in exon 13 of ARID1B (NM_017519.2) predicting a premature stop codon p.(Tyr1132Leufs*67). Sanger sequencing confirmed the heterozygous c.3394_3395insTA mutation in the proband and that it was not present in her parents indicating de novo mutation. Further investigation and new cases will help to understand this phenomenon better.
Department of Child Neurology, Turgut Özal University Faculty of Medicine, Ankara, Turkey.
Fatma Mujgan
FM
Sonmez
Department of Medical Genetics, Health Sciences University, Diskapi Yildirim Beyazit Training and Research Hospital, Ankara, Turkey.
Eyyup
E
Uctepe
Department of Medical Genetics, Turgut Özal University Faculty of Medicine, Ankara, Turkey; Department of Otolaryngology, Turgut Özal University Faculty of Medicine, Ankara, Turkey.
Mehmet
M
Gunduz
Advanced Genomics and Bioinformatics Research Center, The Scientific and Technological Research Council of Turkey (TUBITAK-BILGEM), Kocaeli, Turkey.
Zeliha
Z
Gormez
Department of Dermatology, Turgut Özal University Faculty of Medicine, Ankara, Turkey.
Seval
S
Erpolat
Department of Medical Genetics, Turgut Özal University Faculty of Medicine, Ankara, Turkey.
Murat
M
Oznur
Advanced Genomics and Bioinformatics Research Center, The Scientific and Technological Research Council of Turkey (TUBITAK-BILGEM), Kocaeli, Turkey.
Mahmut Samil
MS
Sagiroglu
Advanced Genomics and Bioinformatics Research Center, The Scientific and Technological Research Council of Turkey (TUBITAK-BILGEM), Kocaeli, Turkey.
Huseyin
H
Demirci
Department of Medical Genetics, Turgut Özal University Faculty of Medicine, Ankara, Turkey.
Esra
E
Gunduz
ARID1B gene; Coffin-Siris syndrome; café-au-lait spots; phenotypic expansion
Pediatr Clin North Am. 2010 Oct;57(5):1131-53
20888463
Am J Med Genet A. 2012 Aug;158A(8):1865-76
22711679
Am J Med Genet C Semin Med Genet. 2014 Sep;166C(3):276-89
25169814
Sci Transl Med. 2012 Jun 13;4(138):138ra78
22700954
Nat Genet. 2012 Mar 18;44(4):376-8
22426308
Am J Hum Genet. 2012 Mar 9;90(3):565-72
22405089
Pediatr Rev. 2001 Mar;22(3):82-90
11230626
Am J Med Genet. 2001 Feb 15;99(1):1-7
11170086
Clin Genet. 2014 Jun;85(6):548-54
23815551
Am J Dis Child. 1970 May;119(5):433-9
5442442
Hum Mutat. 2013 Nov;34(11):1519-28
23929686
Clin Genet. 2012 Sep;82(3):248-55
21801163
Cell Res. 2011 Mar;21(3):396-420
21358755
Nat Genet. 2012 Mar 18;44(4):379-80
22426309
Eur J Hum Genet. 2014 Nov;22(11):1327-9
24569609