title: Array-CGH in unclear syndromic nephropathies identifies a microdeletion in Xq22.3-q23.
abstract: To investigate whether submicroscopic chromosomal deletions or duplications can be causative of unclear syndromic nephropathies, we analyzed ten patients with congenital abnormalities of the kidney and urinary tract or glomerulopathies combined with important extrarenal anomalies by whole-genome array-based comparative genomic hybridization. In a 14-year-old girl presenting with hematuria, proteinuria, mental retardation (MR), sensorineural hearing loss, dysmorphisms, and epilepsy, we detected a microdeletion in chromosome Xq22.3-q23. This deletion was verified and characterized by fluorescence in situ hybridization and multiplex ligation-dependent probe amplification analyses, found to be de novo, uniallelic and 3.3 Mb in size. Electron microscopy of a kidney biopsy showed glomerular basement membrane thinning and segmental splitting of the lamina densa compatible with Alport syndrome. Cranial magnetic resonance and diffusion tensor imaging detected a severe neuronal migration disorder with double cortex formation and pronounced reduction of the fronto-occipital tract system. Thus, in one of ten patients with unclear syndromic nephropathies we identified a previously undescribed contiguous gene syndrome at Xq22.3-q23. The microdeletion contains the X-linked Alport syndrome gene COL4A5, the MR genes FACL4 and PAK3, and parts of the X-chromosomal lissencephaly gene DCX associated with double cortex formation in girls, MR, and epilepsy. The phenotype in our patient combines features of the Alport-MR contiguous gene syndrome with lissencephaly.
authors.affiliation: Institute of Human Genetics, Rheinische Friedrich-Wilhelms-University, Bonn, Germany.
authors.forename: Alexander
authors.initials: A
authors.lastname: Hoischen
authors.forename: Christina
authors.initials: C
authors.lastname: Landwehr
authors.forename: Sarah
authors.initials: S
authors.lastname: Kabisch
authors.forename: Xiao-Qi
authors.initials: XQ
authors.lastname: Ding
authors.forename: Detlef
authors.initials: D
authors.lastname: Trost
authors.forename: Gerhard
authors.initials: G
authors.lastname: Stropahl
authors.forename: Marianne
authors.initials: M
authors.lastname: Wigger
authors.forename: Bernhard
authors.initials: B
authors.lastname: Radlwimmer
authors.forename: Ruthild G
authors.initials: RG
authors.lastname: Weber
authors.forename: Dieter
authors.initials: D
authors.lastname: Haffner
mesh_terms: D000015:Abnormalities, Multiple / Q000235:genetics*; D000293:Adolescent; D001921:Brain / Q000473:pathology; D041321:Chromosomes, Human, X; D055028:Comparative Genomic Hybridization; D004247:DNA / Q000032:analysis; D005260:Female; D017353:Gene Deletion; D006801:Humans; D017404:In Situ Hybridization, Fluorescence; D007674:Kidney Diseases / Q000235:genetics* / Q000473:pathology; D008279:Magnetic Resonance Imaging; D008297:Male; D009394:Nephritis, Hereditary / Q000235:genetics / Q000473:pathology; D020411:Oligonucleotide Array Sequence Analysis; D013577:Syndrome; D014564:Urogenital Abnormalities / Q000235:genetics* / Q000473:pathology
chemical_list: D004247:DNA