TY - JOUR
T1 - Hirschsprung disease as a yet undescribed phenotype in a patient with ARID1B mutation
AU - Takenouchi, Toshiki
AU - Yoshihashi, Hiroshi
AU - Sakaguchi, Yuri
AU - Uehara, Tomoko
AU - Honda, Masataka
AU - Takahashi, Takao
AU - Kosaki, Kenjiro
AU - Miyama, Sahoko
N1 - Funding Information:
We thank Mrs. Yumi Obayashi for her technical assistance in the preparation of this article. This work was supported by Research on rare and intractable diseases from the Ministry of Health, Labour and Welfare, Japan, Initiative on rare and undiagnosed diseases from Japan Agency for Medical Research and Development, Keio University Research Grants for Life Science and Medicine, the Japan Foundation for Pediatric Research Grant No. 14-002, and Grant-in-Aid for Scientific Research (16K09974) from the Japan Society for the Promotion of Science.
Publisher Copyright:
© 2016 Wiley Periodicals, Inc.
PY - 2016/12/1
Y1 - 2016/12/1
N2 - Mutations in the BAF complex (mammalian SWI/SNF complex) are responsible for Coffin-Siris syndrome, which is characterized by developmental delay, distinctive facial features, hirsutism, and hypoplasia/aplasia of the fifth finger/fingernails. Hirschsprung disease is characterized by defective stem cells in the enteric neural system, and the involvement of multiple signaling cascades has been implicated. So far, the roles of the BAF complex in the genesis of Hirschsprung disease have remained unknown. Here, we document a patient with coarse facial features, postnatal growth failure, developmental delay, epilepsy, and hypoplasia of the corpus callosum and cerebellum but without a hypoplastic fifth finger/fingernail. In addition, he had Hirschsprung disease. Exome sequencing with a gene set representing a total of 4,813 genes with known relationships to human diseases revealed a heterozygous frameshift mutation in ARID1B (c.5789delC p.Pro1930Leufs*44). The presence of a congenital cataract and Hirschsprung disease in the presently reported patient further expands the phenotypic spectrum of patients with ARID1B mutations and may suggest the potential role of the BAF complex in the pathogenesis of the enteric neural system. The present observation is in agreement with a recent study of Drosophila neuroblasts showing that the dysregulated BAF complex leads to an abnormal lineage progression of neural stem cell lineages and that Hirschsprung disease is caused by abnormal stem cell lineages in the peripheral neural tissues.
AB - Mutations in the BAF complex (mammalian SWI/SNF complex) are responsible for Coffin-Siris syndrome, which is characterized by developmental delay, distinctive facial features, hirsutism, and hypoplasia/aplasia of the fifth finger/fingernails. Hirschsprung disease is characterized by defective stem cells in the enteric neural system, and the involvement of multiple signaling cascades has been implicated. So far, the roles of the BAF complex in the genesis of Hirschsprung disease have remained unknown. Here, we document a patient with coarse facial features, postnatal growth failure, developmental delay, epilepsy, and hypoplasia of the corpus callosum and cerebellum but without a hypoplastic fifth finger/fingernail. In addition, he had Hirschsprung disease. Exome sequencing with a gene set representing a total of 4,813 genes with known relationships to human diseases revealed a heterozygous frameshift mutation in ARID1B (c.5789delC p.Pro1930Leufs*44). The presence of a congenital cataract and Hirschsprung disease in the presently reported patient further expands the phenotypic spectrum of patients with ARID1B mutations and may suggest the potential role of the BAF complex in the pathogenesis of the enteric neural system. The present observation is in agreement with a recent study of Drosophila neuroblasts showing that the dysregulated BAF complex leads to an abnormal lineage progression of neural stem cell lineages and that Hirschsprung disease is caused by abnormal stem cell lineages in the peripheral neural tissues.
KW - ARID1B
KW - BAF complex
KW - Coffin–Siris syndrome
KW - Hirschsprung disease
KW - SWI/SNF complex
KW - cataract
KW - enteric neural system
KW - stem cell
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U2 - 10.1002/ajmg.a.37861
DO - 10.1002/ajmg.a.37861
M3 - Article
C2 - 27511161
AN - SCOPUS:84994589482
VL - 170
SP - 3249
EP - 3252
JO - American Journal of Medical Genetics, Part A
JF - American Journal of Medical Genetics, Part A
SN - 1552-4825
IS - 12
ER -