TY - JOUR
T1 - Identification of a novel LFNG variant in a Chinese fetus with spondylocostal dysostosis and a systematic review
AU - Wang, Lin
AU - Mizumoto, Shuji
AU - Zhang, Ruixue
AU - Zhang, Yuqi
AU - Liu, Yuan
AU - Cheng, Wenjing
AU - Li, Xin
AU - Dan, Min
AU - Zhang, Chunyan
AU - Gao, Xinru
AU - Wang, Juan
AU - Han, Jiaqi
AU - Jiao, Lianying
AU - Wang, Yating
AU - Jin, Qiujie
AU - Yang, Lihui
AU - Li, Chenxing
AU - Li, Shuxian
AU - Zhu, Jinhui
AU - Jiang, Hai
AU - Nishimura, Gen
AU - Yamada, Takahiro
AU - Yamada, Shuhei
AU - Cai, Na
AU - Qiang, Rong
AU - Guo, Long
N1 - Publisher Copyright:
© The Author(s), under exclusive licence to The Japan Society of Human Genetics 2024.
PY - 2024/7
Y1 - 2024/7
N2 - Spondylocostal dysostosis (SCDO) encompasses a group of skeletal disorders characterized by multiple segmentation defects in the vertebrae and ribs. SCDO has a complex genetic etiology. This study aimed to analyze and identify pathogenic variants in a fetus with SCDO. Copy number variant sequencing and whole exome sequencing were performed on a Chinese fetus with SCDO, followed by bioinformatics analyses, in vitro functional assays and a systematic review on the reported SCDO cases with LFNG pathogenic variants. Ultrasound examinations in utero exhibited that the fetus had vertebral malformation, scoliosis and tethered cord, but rib malformation was not evident. We found a novel homozygous variant (c.1078 C > T, p.R360C) within the last exon of LFNG. The variant was predicted to cause loss of function of LFNG by in silico prediction tools, which was confirmed by an in vitro assay of LFNG enzyme activity. The systematic review listed a total of 20 variants of LFNG in SCDO. The mutational spectrum spans across all exons of LFNG except the last one. This study reported the first Chinese case of LFNG-related SCDO, revealing the prenatal phenotypes and expanding the mutational spectrum of the disorder.
AB - Spondylocostal dysostosis (SCDO) encompasses a group of skeletal disorders characterized by multiple segmentation defects in the vertebrae and ribs. SCDO has a complex genetic etiology. This study aimed to analyze and identify pathogenic variants in a fetus with SCDO. Copy number variant sequencing and whole exome sequencing were performed on a Chinese fetus with SCDO, followed by bioinformatics analyses, in vitro functional assays and a systematic review on the reported SCDO cases with LFNG pathogenic variants. Ultrasound examinations in utero exhibited that the fetus had vertebral malformation, scoliosis and tethered cord, but rib malformation was not evident. We found a novel homozygous variant (c.1078 C > T, p.R360C) within the last exon of LFNG. The variant was predicted to cause loss of function of LFNG by in silico prediction tools, which was confirmed by an in vitro assay of LFNG enzyme activity. The systematic review listed a total of 20 variants of LFNG in SCDO. The mutational spectrum spans across all exons of LFNG except the last one. This study reported the first Chinese case of LFNG-related SCDO, revealing the prenatal phenotypes and expanding the mutational spectrum of the disorder.
UR - https://www.scopus.com/pages/publications/85189363602
U2 - 10.1038/s10038-024-01248-3
DO - 10.1038/s10038-024-01248-3
M3 - 文章
C2 - 38565611
AN - SCOPUS:85189363602
SN - 1434-5161
VL - 69
SP - 321
EP - 327
JO - Journal of Human Genetics
JF - Journal of Human Genetics
IS - 7
ER -