A novel small deletion of LMX1B in a large Chinese family with nail-patella syndrome

• Main Authors: Xiaoyi Yan, Jie Lin, Yifan Wang, Junli Xuan, Ping Yu, Tingwei Guo, Fan Jin
• Format: Article
• Language: English
• Published: BMC 2019-05-01
• Series: BMC Medical Genetics
• Subjects: Bioinformatic analysis; LIM homeobox transcription factor 1-beta (LMX1B); Mutation; Nail–patella syndrome; Sanger sequencing
• Online Access: http://link.springer.com/article/10.1186/s12881-019-0801-3

Abstract Background Nail-patella syndrome (NPS) is an autosomal dominant developmental disorder most commonly characterized by dyplasia of nail or patella, the radial head or the humeral head hypoplasia, and, frequently ocular abnormalities and renal disease. It is caused by heterozygous loss-of-function mutations in the LMX1B gene, which encodes LIM homeodomain transcription factor and is essential for regulating the dorsal limb fate. Methods A five generation pedigree was recruited. Genomic DNA was extracted from the peripheral blood samples. Mutation detection was performed by Sanger sequencing the LMX1B gene. In silico functional annotation of the variant was performed using the in silico predictors SIFT, PolyPhen-2 and Mutation Taster. Results A novel heterozygous small deletion within exon 4 of LMX1B, c.712_714delTTC, was identified in a rare five-generation NPS pedigree. The mutation resulted in a deletion of the conserved amino acid phenylalanine at codon 238 (p.Phe238del), which located in the homeodomain of LMX1B may abolish DNA binding with the molecule. Conformational prediction showed that the variation could transform the helical structure comprising p.Phe234, p.Lys235, p.Ala236, and p.Ser237. Conclusion We identified a novel NPS-causing LMX1B mutation and expanded the spectrum of mutations in the LMX1B gene. The c.712_714delTTC mutation may affect the quaternary structure of LMX1B, which is essential for the specification of dorsal limb fate at both zeugopodal and autopodal levels, leading to typical NPS.