Clinical characteristic and genetic analysis of a new mutation of SF3B4 gene causing neonatal acrofacial dysostosis 1，Nager type

doi:10.3969/j.issn.1673-8640.2025.02.007

Abstract

Abstract:

Objective To investigate the clinical characteristics and genetic etiology of a neonatal acrofacial dysostosis 1，Nager type. Methods Trio-whole-exome sequencing was performed on the patient and her parents，and Sanger sequencing was used for verification. Bioinformatics was used to analyze the pathogenicity of variation. Mutant plasmids were constructed in vitro to observe protein overexpression levels. Results The neonate exhibited distinctive facial appearance at birth，which included downslanting eyelids，ptosis，low-set ears and mandibular hypoplasia，accompanied by neonatal respiratory failure and acidosis. Genetic testing results revealed a frameshift variation in SF3B4 gene，c.980dup（p.G328Rfs*158），which was not present in the parents. The variation was not found in public variation database（dbSNP，1000 Genomes and ExAC）. A search of PubMed and HGMD databases revealed no previous reports of the variation，indicating it is a new variation in SF3B4. The mutated protein was almost not expressed compared to wild-type，indicating that the mutated protein may be degraded caused by SF3B4 c.980dup（p.G328Rfs*158）. Conclusions The clinical characteristics of the patient may be caused by SF3B4 c.980dup（p.G328Rfs*158）. Early molecular diagnosis should be made for children with distinctive facial appearance such as mandibular hypoplasia.

Key words: SF3B4 gene, Acrofacial dysostosis 1, Nager type, Molecular diagnosis

CLC Number:

R446.7

WANG Binbin, LI Fengqi, GUO Fenglian, ZHANG Rui, KANG Huihui, WANG Yuetong. Clinical characteristic and genetic analysis of a new mutation of SF3B4 gene causing neonatal acrofacial dysostosis 1，Nager type[J]. Laboratory Medicine, 2025, 40(2): 142-147.

Figures/Tables 3

References 22

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