title: Deletion Xq27.3q28 in female patient with global developmental delays and skewed X-inactivation.
abstract: BACKGROUND
  Global developmental delay and mental retardation are associated with X-linked disorders including Hunter syndrome (mucopolysaccharidosis type II) and Fragile X syndrome (FXS). Single nucleotide mutations in the iduronate 2-sulfatase (IDS) gene at Xq28 most commonly cause Hunter syndrome while a CGG expansion in the FMR1 gene at Xq27.3 is associated with Fragile X syndrome. Gene deletions of the Xq27-28 region are less frequently found in either condition with rare reports in females. Additionally, an association between Xq27-28 deletions and skewed X-inactivation of the normal X chromosome observed in previous studies suggested a primary role of the Xq27-28 region in X-inactivation.
  
  
  METHODS
  We describe the clinical, molecular and biochemical evaluations of a four year-old female patient with global developmental delay and a hemizygous deletion of Xq27.3q28 (144,270,614-154,845,961 bp), a 10.6 Mb region that contains >100 genes including IDS and FMR1. A literature review revealed rare cases with similar deletions that included IDS and FMR1 in females with developmental delay, variable features of Hunter syndrome, and skewed X-inactivation of the normal X chromosome. In contrast, our patient exhibited skewed X-inactivation of the deleted X chromosome and tested negative for Hunter syndrome.
  
  
  CONCLUSIONS
  This is a report of a female with a 10.6 Mb Xq27-28 deletion with skewed inactivation of the deleted X chromosome. Contrary to previous reports, our observations do not support a primary role of the Xq27-28 region in X-inactivation. A review of the genes in the deletion region revealed several potential genes that may contribute to the patient's developmental delays, and sequencing of the active X chromosome may provide insight into the etiology of this clinical presentation.
authors: Lauren S
authors: LS
authors: Marshall
authors: Julie
authors: J
authors: Simon
authors: Tim
authors: T
authors: Wood
authors: Mei
authors: M
authors: Peng
authors: Renius
authors: R
authors: Owen
authors: Gary S
authors: GS
authors: Feldman
authors: Michael V
authors: MV
authors: Zaragoza
mesh_terms: D002140:California; D002675:Child, Preschool; D002872:Chromosome Deletion; D041321:Chromosomes, Human, X; D055028:Comparative Genomic Hybridization; D002658:Developmental Disabilities / Q000235:genetics*; D005260:Female; D051860:Fragile X Messenger Ribonucleoprotein 1 / Q000235:genetics; D005600:Fragile X Syndrome / Q000175:diagnosis / Q000235:genetics*; D006801:Humans; D010641:Phenotype; D049951:X Chromosome Inactivation
chemical_list: D051860:Fragile X Messenger Ribonucleoprotein 1
references: Am J Hum Genet. 1995 May;56(5):1108-15
references: 7726166
references: Nat Genet. 1996 Jun;13(2):175-82
references: 8640223
references: Hum Mol Genet. 1995 Sep;4(9):1681-4
references: 8541863
references: Am J Hum Genet. 2010 Feb 12;86(2):185-95
references: 20159109
references: Pathogenetics. 2008 Nov 03;1(1):4
references: 19014668
references: Hum Genet. 1990 Mar;84(4):347-52
references: 2307456
references: Am J Hum Genet. 2002 May;70(5):1349-56
references: 11898126
references: Am J Med Genet. 1992 Sep 1;44(1):100-3
references: 1355630
references: Hum Mol Genet. 2004 Aug 15;13(16):1763-73
references: 15229184
references: Nat Genet. 1992 Aug;1(5):341-4
references: 1302032
references: Am J Med Genet A. 2012 May;158A(5):1055-9
references: 22492741
references: Hum Mutat. 1998;11(2):121-6
references: 9482575
references: Hum Genet. 2000 Oct;107(4):343-9
references: 11129333
references: Hum Genet. 2000 Oct;107(4):304-11
references: 11129329
references: Hum Mol Genet. 2012 Oct 15;21(20):4497-507
references: 22814392
references: Am J Hum Genet. 1995 May;56(5):1042-51
references: 7726157
references: Nat Genet. 1998 Jun;19(2):134-9
references: 9620768
references: Am J Hum Genet. 2012 Apr 6;90(4):579-90
references: 22482801
references: Nat Rev Genet. 2005 Jan;6(1):46-57
references: 15630421
references: Am J Med Genet A. 2007 Jun 15;143A(12):1358-65
references: 17506108
references: Nat Genet. 1999 Oct;23(2):185-8
references: 10508514
references: Genomics. 1992 Jul;13(3):543-50
references: 1639384
references: Science. 1991 Jun 21;252(5013):1711-4
references: 1675488
references: Clin Genet. 1990 May;37(5):355-62
references: 2112988
references: Am J Med Genet. 1992 Apr 15-May 1;43(1-2):279-81
references: 1605201
references: Am J Hum Genet. 2012 Oct 5;91(4):694-702
references: 23000143
references: Hum Mol Genet. 2001 Sep 15;10(19):2171-9
references: 11590134
references: Hum Mol Genet. 1994 Apr;3(4):615-20
references: 8069307
references: Blood. 1994 May 15;83(10):2899-905
references: 8180385
references: Am J Hum Genet. 1992 Dec;51(6):1229-39
references: 1281384
references: Am J Hum Genet. 1992 Aug;51(2):316-22
references: 1642233
references: Cell. 1991 May 31;65(5):905-14
references: 1710175
references: Nature. 2005 Mar 17;434(7031):400-4
references: 15772666
references: Hum Mol Genet. 1996 Nov;5(11):1777-83
references: 8923006
references: Am J Hum Genet. 2004 Jul;75(1):97-105
references: 15154114