Alagille syndrome is a multisystem disorder with an autosomic dominant pattern of inheritance that affects the liver, heart, eyes, kidneys, skeletal system and presents characteristic facial features. Mutations of the JAG1 gene have been identified in 20-89% of the patients with Alagille syndrome, this gene encodes for a ligand that activates the Notch signaling pathway. In the present study we analyzed 9 Mexican patients with Alagille syndrome who presented the clinical criteria for the classical presentation of the disease. By using the denaturing high performance liquid chromatography mutation analysis we were able to identify different mutations in 7 of the patients (77.77%), importantly, we found 5 novel mutations in JAG1 gene. The allelic frequency distribution of 13 polymorphisms in Mexican population is also reported. The overall results demonstrated an expanding mutational spectrum of JAG1 gene in the Mexican population.
Keywords: AA, African American; ALGS, Alagille syndrome; Alagille syndrome; CEU, Utah Residents with Northern and Western European Ancestry; CHB, Han Chinese in Beijing, China; CI, confidence interval; DHPLC, Denaturing high performance liquid chromatography; DSL, Delta-Serrate-Lag2 domain; EA, European American; ESP, Exome Sequencing Project; HGMD, The Human Gene Mutation Database; HWE, Hardy–Weinberg Equilibrium; JAG1 mutations; JAG1, Gene coding for JAGGED1 protein; JPT, Japanese in Tokyo, Japan; LOVD, Leiden Open Variation Database; MAF, minor allele frequency; MEX, Mexican population; MIM, Mendelian Inheritance in Man; Mexican patients; NA, not applicable; ND, not determined; NMD, Nonsense Mediated mRNA Decay; NOTCH2, gene coding for NOTCH2 protein; OR, odds ratio; PCR, polymerase chain reaction; YRI, Yoruba in Ibadan, Nigeria; dbSNP, The Single Nucleotide Polymorphism Database; kb, kilobase(s) or 1000 bp; mutDB, mutDB Polymorphism Database.