Identification of a Novel NLRP12 Nonsense Mutation (Trp408X) in the Extremely Rare Disease FCAS by Exome Sequencing.
Familial cold autoinflammatory syndrome (FCAS) is an extremely rare autosomal dominant inherited disease. Although there are four genes that have been linked with FCAS, its molecular diagnosis has been challenging in a relatively large proportion of cases. In this study, we aimed to investigate the genetic defect of a recruited FCAS family using exome sequencing followed by in-depth bioinformatics analysis. As a result, a novel heterozygous stop-gain mutation (Trp408X) in NLRP12 was identified in autosomal dominant inherited FCAS with clinical features of recurrent fever and skin urticaria due to cold conditions. When combined with previous studies, all of the reported mutations were found to have occurred in a highly conserved region in the NACHT domain coding sequence in NLRP12 exon 3, suggesting that a screening strategy for FCAS should focus on this area of the gene. In conclusion, this study demonstrates the importance of exome sequencing for clinical diagnosis of genetic disorders and provides molecular insight into FCAS treatment and diagnosis.
Department of Rheumatology, the First Affiliated Hospital of Wenzhou Medical University, Wenzhou, China.
Xiaoru
X
Xia
Department of Pneumology, the First Affiliated Hospital of Wenzhou Medical University, Wenzhou, China.
Caijun
C
Dai
Department of Rheumatology, the First Affiliated Hospital of Wenzhou Medical University, Wenzhou, China.
Xiaochun
X
Zhu
Department of Rheumatology, the First Affiliated Hospital of Wenzhou Medical University, Wenzhou, China.
Qiumei
Q
Liao
Department of Wounds and Burns, the First Affiliated Hospital of Wenzhou Medical University, Wenzhou, China.
Xu
X
Luo
Department of Pneumology, the First Affiliated Hospital of Wenzhou Medical University, Wenzhou, China.
Yangyang
Y
Fu
Department of Pneumology, the First Affiliated Hospital of Wenzhou Medical University, Wenzhou, China.
Liangxing
L
Wang
D000328:Adult; D000368:Aged; D001327:Autoimmune Diseases / Q000175:diagnosis / Q000235:genetics* / Q000473:pathology; D002648:Child; D018389:Codon, Nonsense / Q000235:genetics; D056587:Cryopyrin-Associated Periodic Syndromes / Q000235:genetics* / Q000473:pathology; D059472:Exome / Q000235:genetics; D005091:Exons / Q000235:genetics; D005260:Female; D006579:Heterozygote; D059014:High-Throughput Nucleotide Sequencing; D006801:Humans; D047908:Intracellular Signaling Peptides and Proteins / Q000235:genetics*; D008297:Male; D020125:Mutation, Missense / Q000235:genetics; D010375:Pedigree; D011487:Protein Conformation; D035583:Rare Diseases / Q000175:diagnosis / Q000235:genetics* / Q000473:pathology; D012867:Skin / Q000378:metabolism / Q000473:pathology; D014581:Urticaria / Q000235:genetics* / Q000473:pathology
D018389:Codon, Nonsense; D047908:Intracellular Signaling Peptides and Proteins; C476731:NLRP12 protein, human