BMP2 is a potential causative gene for isolated dextrocardia situs solitus

Analia Yogi; Ryosei Iemura; Hisae Nakatani; Kei Takasawa; Maki Gau; Takeru Yamauchi; Masayuki Yoshida; Keiji Moriyama; Taku Ishii; Susumu Hosokawa; Mamiko Yamada; Hisato Suzuki; Kenjiro Kosaki; Kenichi Kashimada; Tomohiro Morio

doi:10.1016/j.ejmg.2023.104820

BMP2 is a potential causative gene for isolated dextrocardia situs solitus

Eur J Med Genet. 2023 Sep;66(9):104820. doi: 10.1016/j.ejmg.2023.104820. Epub 2023 Aug 11.

Authors

Affiliations

¹ Department of Pediatrics and Developmental Biology, Tokyo Medical and Dental University, 1-5-45 Yushima, Bunkyo-ku, Tokyo, 113-8510, Japan.
² Neonatal Intensive Care Unit, Tsuchiura General Hospital, Ibaraki, Japan.
³ Department of Medical Genetics, Tokyo Medical and Dental University, 1-5-45 Yushima, Bunkyo-ku, Tokyo, 113-8510, Japan.
⁴ Department of Maxillofacial Orthognathics, Tokyo Medical and Dental University, 1-5-45 Yushima, Bunkyo-ku, Tokyo, 113-8510, Japan.
⁵ Center for Medical Genetics, Keio University School of Medicine, 35 Shinanomachi, Shinjuku-ku, Tokyo, 160-8582, Japan.
⁶ Department of Pediatrics and Developmental Biology, Tokyo Medical and Dental University, 1-5-45 Yushima, Bunkyo-ku, Tokyo, 113-8510, Japan. Electronic address: kkashimada.ped@tmd.ac.jp.

PMID: 37572998
DOI: 10.1016/j.ejmg.2023.104820

Abstract

BMP2 (bone morphogenic protein-2) is a member of the TGF-β superfamily and has essential roles in the development of multiple organs, including osteogenesis. Because of its crucial role in organ and skeletal development, Bmp2 null mice is fetal lethal. The recent report has characterized multiple patients with BMP2 haploinsufficiency, describing individuals with BMP2 sequence variants and deletions associated with short stature without endocrinological abnormalities, a recognizable craniofacial gestalt, skeletal anomalies, and congenital heart disease. However, due to a small number of reported patients with BMP2 haploinsufficiency, the genotype and phenotype correlations are not fully understood. We experienced a family of BMP2 haploinsufficiency with a novel frameshift variant NM_001200.4: c.231dup (p.Tyr78Leufs*38) which was predicted to be "pathogenic" by the American College of Genetics and Genomics (ACGM) criteria. In addition to short stature, impaired hearing ability and minor skeletal deformities, the proband exhibited isolated dextrocardia situs solitus without cardiac anomalies and abnormal locations of other visceral organs. Our study would shed light on the crucial role of BMP2 in determining the cardiac axis, and further studies are needed to assemble more cases to elucidate BMP2 role in human heart development.

Keywords: 20p12.3 microdeletion syndrome; Bone morphogenetic protein-2; Dextrocardia situs solitus; Whole-exome sequencing.

MeSH terms

Animals
Bone Morphogenetic Protein 2 / genetics
Dextrocardia* / diagnostic imaging
Dextrocardia* / genetics
Dwarfism*
Family
Genotype
Heart Defects, Congenital* / genetics
Humans
Mice
Transforming Growth Factor beta / genetics

Substances

Transforming Growth Factor beta
BMP2 protein, human
Bone Morphogenetic Protein 2