Dataset Information

A novel variant of GLI3, p.Asp1514Thrfs*5, is identified in a Chinese family affected by polydactyly.

ABSTRACT: Polydactyly is a common congenital malformation characterized by the presence of supernumerary fingers or toes. In this case study, we sought to identify the causative pathogenic factor in a family from a northern region of China affected by non-syndromic postaxial polydactyly (PAP). After recruiting a three-generation family with PAP, whole-exome sequencing was performed to identify the causative variant. In silico analysis and Sanger sequencing were used to validate the variant. We identified a novel heterozygous frameshift variant (NM_000168.6:c.4540delG, p.Asp1514Thrfs*5) in the transcriptional activator (TA1) domain of the GLI3 gene. The novel frameshift variant identified in this study further confirms the relationship between non-syndromic PAP and GLI3 and extends the previously established mutational and phenotypic spectra of GLI3.

SUBMITTER: Wang Y

PROVIDER: S-EPMC9266609 | biostudies-literature | 2022 Jul

REPOSITORIES: biostudies-literature

ACCESS DATA

Publications

A novel variant of GLI3, p.Asp1514Thrfs*5, is identified in a Chinese family affected by polydactyly.

Wang Yusi Y Hao Xuguang X Jia Xueyuan X Ji Wei W Yuan Shuai S Gnamey Estelle Judith Abla EJA Huang Min M Xu Lidan L Zhang Xuelong X Bai Jing J Sun Wenjing W Fu Songbin S Liu Yong Y Wu Jie J

Molecular genetics & genomic medicine 20220512 7

<h4>Background</h4>Polydactyly is a common congenital malformation characterized by the presence of supernumerary fingers or toes. In this case study, we sought to identify the causative pathogenic factor in a family from a northern region of China affected by non-syndromic postaxial polydactyly (PAP).<h4>Methods</h4>After recruiting a three-generation family with PAP, whole-exome sequencing was performed to identify the causative variant. In silico analysis and Sanger sequencing were used to va ...[more]

PMID: 35546307

Similar Datasets

Project description:BackgroundLethal respiratory failure is primarily caused by a deficiency of pulmonary surfactant, and is the main cause of neonatal death among preterm infants. Pulmonary surfactant metabolism dysfunction caused by variants in the ABCA3 gene is a rare disease with very poor prognosis. Currently, the mechanisms associated with some ABCA3 variants have been determined, including protein mistrafficking and impaired phospholipid transport. However, some novel variants and their underlying pathogenesis has not been fully elucidated yet. In this study we aimed to identify the genetic features in a family with lethal respiratory failure.MethodsWe studied members of two generations of a Chinese family, including a female proband, her parents, her monozygotic twin sister, and her older sister. Trio whole exome sequencing (WES) were used on the proband and her parents to identify the ABCA3 variants. Sanger sequencing and real-time quantitative polymerase chain reaction (PCR) were used on the monozygotic twin sister of proband to validate the ABCA3 synonymous variant and exon deletion, respectively. The potential pathogenicity of the identified synonymous variant was predicted using the splice site algorithms dbscSNV11_AdaBoost, dbscSNV11_RandomForest, and Human Splicing Finder (HSF).ResultsAll patients showed severe respiratory distress, which could not be relieved by mechanical ventilation, supplementation of surfactant, or steroid therapy, and died at an early age. WES analysis revealed that the proband had compound heterozygous ABCA3 variants, including a novel synonymous variant c.G873A (p.Lys291Lys) in exon 8 inherited from the mother, and a heterozygous deletion of exons 4-7 inherited from the father. The synonymous variant was consistently predicted to be a cryptic splice donor site that may lead to aberrant splicing of the pre-mRNA by three different splice site algorithms. The deletion of exons 4-7 of the ABCA3 gene was determined to be a likely pathogenic variant. The variants were confirmed in the monozygotic twin sister of proband by Sanger sequencing and qPCR respectively. The older sister of proband was not available to determine if she also carried both ABCA3 variants, but it is highly likely based on her clinical course.ConclusionsWe identified a novel synonymous variant and a deletion in the ABCA3 gene that may be responsible for the pathogenesis in patients in this family. These results add to the known mutational spectrum of the ABCA3 gene. The study of ABCA3 variants may be helpful for the implementation of patient-specific therapies.

Dataset Information

A novel variant of GLI3, p.Asp1514Thrfs*5, is identified in a Chinese family affected by polydactyly.

Publications

A novel variant of GLI3, p.Asp1514Thrfs*5, is identified in a Chinese family affected by polydactyly.

Similar Datasets

OmicsDI is part of the ELIXIR infrastructure

Tweets