Identification of a Novel de Novo Variant in the CASZ1 Causing a Rare Type of Dilated Cardiomyopathy

Abstract

A new de novo frameshift variant has been identified in the CASZ1 gene leading to severe dilated cardiomyopathy. Methods: The proband was analyzed with WES NGS, post-mortem, using dried blood spots on filters. The variant was verified with Sanger sequencing for the proband and her parents. Results: We reported a proband with a new de novo frameshift mutation, c.3781del (p.(Trp1261GlyfsTer29)), in the CASZ1 gene. The clinical presentation was similar to the severe phenotype described in previous studies. Conclusions: In this study, we described a new case with a frameshift mutation in CASZ1 causing a severe phenotype of dilated cardiomyopathy.

Sarcomere gene variants did not improve cardiac function in pediatric patients with dilated cardiomyopathy from Japanese cohorts

“…28 Currently, this gene has only three known variants, namely, Leu38Pro, Lys351Term, and Val815Profs*15. [29][30][31][32] All of these are loss-of-function variants located in the coding region and may be associated with DCM. CASZ1 variants may result in haploinsu ciency caused by nonsense-mediated decay, which is important in the pathological mechanism of DCM.…”

Sarcomere gene variants did not improve cardiac function in pediatric patients with dilated cardiomyopathy from Japanese cohorts

“…Keiichi Hirono 1 , MD, PhD, Yukiko Hata 2 , PhD, Shojiro Ichimata 2 , MD, PhD, Naoki Nishida 2 , MD, PhD, Teruhiko Imamura 3 , MD, PhD, Yoshihiro Asano 4 , MD, PhD, Yuki Kuramoto 5 , MD, PhD, Kaori Tsuboi 1 , MD, Shinya Takarada 1 , MD, PhD, Mako Okabe 1 , MD, MD, Hideyuki Nakaoka 1 , MD, PhD, Keijiro Ibuki 1 , MD, PhD, Sayaka Ozawa 1 , MD, PhD, Jun Muneuchi 6 , MD, PhD, Kazushi Yasuda 7 , MD, PhD, Kotaro Urayama 8 , MD, Hideharu Oka 9 , MD, PhD, Tomoyuki Miyamoto 10 , MD, PhD, Kenji Baba 11 , MD, PhD, Akio Kato 12 , MD, Hirofumi Saiki 13 , MD, PhD, Naoki Kuwahara 14 , MD, PhD, Masako Harada 15 , MD, PhD, Shiro Baba 16 , MD, PhD, Mari Morikawa 17 , MD, PhD, Hidenori Iwasaki 18 , MD, PhD, Yuichiro Hirata 19 , MD, Yuki Ito 20 , MD, Heima Sakaguchi 20 , MD, PhD, Susumu Urata 21 , MD, PhD, Koichi Toda 22 , MD, PhD, Emi Kittaka 23 , MD, Seigo Okagda 24 , MD, PhD, Yohei Hasebe 25 , MD, PhD, Shinsuke Hoshino 26 , MD, PhD, Takanari Fujii 27 , MD, PhD, Norie Mitsushita 28 , MD, Masaki Nii 28 , MD, PhD, Kayo Ogino 29 , MD, PhD, Mitsuhiro Fujino 30 , MD, PhD, Yoko Yoshida 31 , MD, PhD, Yutaka Fukuda 32 , MD, PhD, Satoru Iwashima 33 , MD, PhD, Kiyohiro Takigiku 34 , MD, PhD, Yasushi Sakata 35 , MD, PhD, Ryo Inuzuka 36 , MD, PhD, Jun Maeda 37 , MD,…”

“…32 Only 3 variants have been described (Leu38Pro, Lys351Term, and Val815Profs*15). [33][34][35][36] All of these are loss-of-function variants located in the coding region and may be associated with DCM. CASZ1 variants may result in haploinsufficiency due to nonsense-mediated decay, which plays an important role in the pathological mechanism of DCM.…”

Role of the CASZ1 transcription factor in tissue development and disease

“…Additionally, a novel variant of the CASZ1 gene, c.2443_2459delGTGGGCACCCCCAGCCT (p.Val815Profs*14), was identified in a patient with DCM and left ventricular noncompaction cardiomyopathy (LVNC), highlighting the role of CASZ1 as a pathogenic gene for human LVNC [ 24 ]. In another case of DCM, a de novo frameshift mutation, c.3781del (p.(Trp1261GlyfsTer29)), was identified in the CASZ1 gene [ 25 ]. Associating CASZ1 loss-of-function mutations with human cardiac disease susceptibility holds potential implications for the personalized prevention and treatment of cardiac diseases.…”

“…Therefore, CASZ1 plays dual biological roles in diverse tumors. Beyond cancer, loss-of-function mutations in CASZ1 have been associated with susceptibility to human heart diseases [22][23][24][25], and CASZ1 methylation has been associated with cardiovascular mortality [26]. Additionally, CASZ1 has been implicated in osteoarthritis, immune inflammatory, and regulatory responses [27].…”