Alu-mediated deletion of PIGL in a Patient with CHIME syndrome

作者：Johnson Amy Knight; Schaefer Gerald Bradley^*; Lee Jennifer; Hu Ying; del Gaudio Daniela

来源：American Journal of Medical Genetics, Part A, 2017, 173(5): 1378-1382.

DOI：10.1002/ajmg.a.38181

• chromosomal microarray
• ichthyosis
• novel mutation
• Zunich ectodermal syndrome

CHIME syndrome is a rare autosomal recessive neuroectodermal disorder associated with biallelic mutations in PIGL. To date, six molecularly confirmed cases of CHIME syndrome have been reported. Here, we report the seventh patient with biallelic PIGL mutations associated with CHIME syndrome and describe the first characterization of an intragenic deletion in PIGL. Our characterization of the deletion breakpoint junction demonstrated that the breakpoints occurred within Alu repeats and the deletion was most likely mediated by a microhomology event. Analysis of PIGL genomic sequences for repetitive elements demonstrated that Alu repeats represent approximate to 34% of its intronic sequence, suggesting that the genomic architecture may predispose the gene to disease-causing copynumber changes. Taken together, these findings indicate that patients with a clinical diagnosis of CHIME syndrome and a single identifiable mutation in PIGL warrant further investigation for copynumber changes involving PIGL.

• 出版日期2017-5