title: Severe Alport syndrome in a young woman caused by a t(X;1)(q22.3;p36.32) balanced translocation.
abstract: The course of renal involvement and hearing loss is much milder in most female X-linked Alport syndromes than in male patients. We examined the molecular mechanism of development of the disease in a female patient with severe Alport syndrome. The patient showed heavy proteinuria, hematuria, neurosensory hearing loss and primary amenorrhea. Renal biopsy findings of electron microscopy and immunostaining of the alpha5 chain of type IV collagen indicated a female X-linked Alport syndrome. G-banding chromosomal analysis showed a t(X;1)(q22.3;p36.32) balanced translocation. Analysis of the collagen type IV (COL4A5) gene by genomic DNA sequencing, complementary DNA (cDNA) sequencing and multiplex ligation-dependent probe amplification assay showed no mutations or deletions/duplications of the gene. However, fluorescence in situ hybridization using the probes for exon 1 and exon 51 of the COL4A5 gene showed disruption of one copy of the gene. Replication R-banding chromosomal analysis indicated preferential inactivation of the normal X chromosome. This is the first report of severe Alport syndrome in a female patient carrying a balanced translocation between the chromosome X and 1 producing the disruption of one copy of COL4A5 gene and silencing of the other copy because of preferential inactivation of the normal X chromosome. Chromosomal abnormalities should be considered in female patients with severe forms of Alport syndrome.
authors.affiliation: Department of Pediatrics, Division of Child Health and Development, Kobe University Graduate School of Medicine, 7-5-2 Kusunoki-Cho, Chuo-ku, Kobe, 650-0017, Japan. iijima@med.kobe-u.ac.jp
authors.forename: Kazumoto
authors.initials: K
authors.lastname: Iijima
authors.forename: Kandai
authors.initials: K
authors.lastname: Nozu
authors.forename: Koichi
authors.initials: K
authors.lastname: Kamei
authors.forename: Makiko
authors.initials: M
authors.lastname: Nakayama
authors.forename: Shuichi
authors.initials: S
authors.lastname: Ito
authors.forename: Kentaro
authors.initials: K
authors.lastname: Matsuoka
authors.forename: Tsutomu
authors.initials: T
authors.lastname: Ogata
authors.forename: Hiroshi
authors.initials: H
authors.lastname: Kaito
authors.forename: Koichi
authors.initials: K
authors.lastname: Nakanishi
authors.forename: Masafumi
authors.initials: M
authors.lastname: Matsuo
mesh_terms: D000293:Adolescent; D002648:Child; D002675:Child, Preschool; D002878:Chromosomes, Human, Pair 1 / Q000235:genetics*; D041321:Chromosomes, Human, X / Q000235:genetics*; D024141:Collagen Type IV / Q000235:genetics*; D005260:Female; D006801:Humans; D007150:Immunohistochemistry; D017404:In Situ Hybridization, Fluorescence; D046529:Microscopy, Electron, Transmission; D009394:Nephritis, Hereditary / Q000235:genetics* / Q000473:pathology; D016133:Polymerase Chain Reaction; D014178:Translocation, Genetic / Q000235:genetics*; D055815:Young Adult
chemical_list: C478159:COL4A5 protein, human; D024141:Collagen Type IV
references.citation: Proc Natl Acad Sci U S A. 1991 Aug 1;88(15):6848-52
references.pmid: 1862109
references.citation: Hum Genet. 1995 Jun;95(6):607-29
references.pmid: 7789944
references.citation: Br Med J. 1927 Mar 19;1(3454):504-6
references.pmid: 20773074
references.citation: Hum Genet. 1990 Oct;85(5):455-61
references.pmid: 2227929
references.citation: Trends Genet. 1994 Jul;10(7):230-5
references.pmid: 8091502
references.citation: Am J Hum Genet. 1992 Aug;51(2):291-8
references.pmid: 1642230
references.citation: Lancet. 1988 Oct 29;2(8618):1005-7
references.pmid: 2902439
references.citation: J Med Genet. 1993 Mar;30(3):177-84
references.pmid: 8097254
references.citation: Lab Invest. 1972 Nov;27(5):473-87
references.pmid: 4653971
references.citation: Am J Med Genet. 1992 Jan 15;42(2):161-9
references.pmid: 1733164
references.citation: J Am Soc Nephrol. 1998 Aug;9(8):1433-40
references.pmid: 9697665
references.citation: Am J Hum Genet. 1992 Dec;51(6):1229-39
references.pmid: 1281384
references.citation: J Am Soc Nephrol. 2008 Nov;19(11):2052-9
references.pmid: 18448583
references.citation: Adv Nephrol Necker Hosp. 1993;22:15-35
references.pmid: 8427057
references.citation: Hum Reprod. 2006 Jun;21(6):1477-83
references.pmid: 16497693
references.citation: Am J Med Genet. 1996 Jul 12;64(1):27-30
references.pmid: 8826444
references.citation: Am J Kidney Dis. 1999 Nov;34(5):854-62
references.pmid: 10561141
references.citation: Nephrol Dial Transplant. 1997 Jun;12(6):1238-41
references.pmid: 9198058
references.citation: Arch Pathol. 1973 Jun;95(6):374-9
references.pmid: 4701392
references.citation: Am J Pathol. 1972 Nov;69(2):213-24
references.pmid: 4343992
references.citation: J Am Soc Nephrol. 2003 Oct;14(10):2603-10
references.pmid: 14514738