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

• Published in: BMC medical genetics 2019-05, Vol.20 (1), p.71-71, Article 71
• Main Authors: Yan, Xiaoyi, Lin, Jie, Wang, Yifan, Xuan, Junli, Yu, Ping, Guo, Tingwei, Jin, Fan
• Format: Article
• Language: English
• Subjects: Amino acids; Analysis; Bioinformatic analysis; Causes of; China; Codon; Codons; Deoxyribonucleic acid; Developmental disabilities; Diagnosis; DNA; DNA binding; DNA sequencing; Exons; Eye diseases; Family; Female; Gene Deletion; Gene mutation; Genes; Genetic aspects; Genetic testing; Genetics; Genomics; Glaucoma; Health aspects; Hereditary diseases; Heterozygote; Homeobox; Humans; Humerus; Hypoplasia; Kidney diseases; LIM homeobox transcription factor 1-beta (LMX1B); LIM-Homeodomain Proteins - genetics; LMX1B gene; Loss of Function Mutation; Male; Males; Medical schools; Mutation; Nail-patella syndrome; Nail-Patella Syndrome - genetics; Novels; Patients; Pedigree; Peripheral blood; Phenylalanine; Protein structure; Proteins; Quaternary structure; Sanger sequencing; Transcription (Genetics); Transcription factors; Transcription Factors - genetics
• ISSN: 1471-2350; 1471-2350
• DOI: 10.1186/s12881-019-0801-3

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. 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. 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. 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.