title: Alu-mediated deletion of PIGL in a Patient with CHIME syndrome.
abstract: 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 ∼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.
authors.affiliation: Department of Human Genetics, University of Chicago, Chicago, Illinois.
authors.forename: Amy
authors.initials: A
authors.lastname: Knight Johnson
authors.affiliation: Section of Genetics and Metabolism, Arkansas Children's Hospital, Little Rock, Arkansas.
authors.forename: Gerald Bradley
authors.identifier: http://orcid.org/0000-0002-1236-0017
authors.initials: GB
authors.lastname: Schaefer
authors.affiliation: Greenwood Genetic Center, Greenwood, South Carolina.
authors.forename: Jennifer
authors.initials: J
authors.lastname: Lee
authors.affiliation: Department of Human Genetics, University of Chicago, Chicago, Illinois.
authors.forename: Ying
authors.initials: Y
authors.lastname: Hu
authors.affiliation: Department of Human Genetics, University of Chicago, Chicago, Illinois.
authors.forename: Daniela
authors.initials: D
authors.lastname: Del Gaudio
mesh_terms: D000483:Alleles; D020087:Alu Elements / Q000235:genetics*; D002675:Child, Preschool; D003103:Coloboma / Q000235:genetics* / Q000503:physiopathology; D006314:Hearing Loss, Conductive / Q000235:genetics* / Q000503:physiopathology; D006330:Heart Defects, Congenital / Q000235:genetics* / Q000503:physiopathology; D006801:Humans; D007057:Ichthyosis / Q000235:genetics* / Q000503:physiopathology; D008607:Intellectual Disability / Q000235:genetics* / Q000503:physiopathology; D007438:Introns; D008297:Male; D017351:N-Acetylglucosaminyltransferases / Q000235:genetics*; D020752:Neurocutaneous Syndromes / Q000235:genetics* / Q000503:physiopathology; D017384:Sequence Deletion / Q000235:genetics*
chemical_list: D017351:N-Acetylglucosaminyltransferases; C000603519:PIGL protein, human
keywords: Zunich ectodermal syndrome; chromosomal microarray; ichthyosis; novel mutation