title: Genotype-phenotype characterization in 13 individuals with chromosome Xp11.22 duplications.
abstract: We report 13 new individuals with duplications in Xp11.22-p11.23. The index family has one male and two female members in three generations with mild-severe intellectual disability (ID), speech delay, dysmorphic features, early puberty, constipation, and/or hand and foot abnormalities. Affected individuals were found to have two small duplications in Xp11.22 at nucleotide position (hg19) 50,112,063-50,456,458 bp (distal) and 53,160,114-53,713,154 bp (proximal). Collectively, these two regions include 14 RefSeq genes, prompting collection of a larger cohort of patients, in an attempt to delineate critical genes associated with the observed phenotype. In total, we have collected data on nine individuals with duplications overlapping the distal duplication region containing SHROOM4 and DGKK and eight individuals overlapping the proximal region including HUWE1. Duplications of HUWE1 have been previously associated with non-syndromic ID. Our data, with previously published reports, suggest that duplications involving SHROOM4 and DGKK may represent a new syndromic X-linked ID critical region associated with mild to severe ID, speech delay +/- dysarthria, attention deficit disorder, precocious puberty, constipation, and motor delay. We frequently observed foot abnormalities, 5th finger clinodactyly, tapering fingers, constipation, and exercise intolerance in patients with duplications of these two genes. Regarding duplications including the proximal region, our observations agree with previous studies, which have found associations with intellectual disability. In addition, expressive language delay, failure to thrive, motor delay, and 5th finger clinodactyly were also frequently observed in patients with the proximal duplication.
authors.affiliation: Department of Medical Genetics, Kaiser Permanente, San Francisco, California.
authors.forename: Sarah E
authors.initials: SE
authors.lastname: Grams
authors.affiliation: Alberta Children's Hospital Research Institute for Child and Maternal Health, Alberta, Canada.
authors.forename: Bob
authors.initials: B
authors.lastname: Argiropoulos
authors.affiliation: Department of Genetics, Children's Hospital of Eastern Ontario, Ottawa, Ontario, Canada.|Department of Pediatrics, University of Ottawa, Ottawa, Ontario, Canada.
authors.forename: Matthew
authors.initials: M
authors.lastname: Lines
authors.affiliation: Department of Genetics, Children's Hospital of Eastern Ontario, Ottawa, Ontario, Canada.|Department of Pediatrics, University of Ottawa, Ottawa, Ontario, Canada.
authors.forename: Pranesh
authors.initials: P
authors.lastname: Chakraborty
authors.affiliation: Department of Genetics, Children's Hospital of Eastern Ontario, Ottawa, Ontario, Canada.
authors.forename: Jean
authors.initials: J
authors.lastname: Mcgowan-Jordan
authors.affiliation: Department of Genetics, Children's Hospital of Eastern Ontario, Ottawa, Ontario, Canada.|Department of Pediatrics, University of Ottawa, Ottawa, Ontario, Canada.
authors.forename: Michael T
authors.initials: MT
authors.lastname: Geraghty
authors.affiliation: Department of Genetics, Sutter Memorial Hospital, Sacramento, California.
authors.forename: Marilyn
authors.initials: M
authors.lastname: Tsang
authors.affiliation: Department of Genetics, Sutter Memorial Hospital, Sacramento, California.
authors.forename: Marthand
authors.initials: M
authors.lastname: Eswara
authors.affiliation: Department of Genetics, Kaiser Permanente, Sacramento, California.
authors.forename: Kamer
authors.initials: K
authors.lastname: Tezcan
authors.affiliation: Department of Genetics, Kaiser Permanente, Sacramento, California.
authors.forename: Kelly L
authors.initials: KL
authors.lastname: Adams
authors.affiliation: Department of Medical Genetics, Kaiser Permanente, Portland, Oregon.
authors.forename: Leesa
authors.initials: L
authors.lastname: Linck
authors.affiliation: Department of Medical Genetics, Kaiser Permanente, Portland, Oregon.
authors.forename: Patricia
authors.initials: P
authors.lastname: Himes
authors.affiliation: Department of Medical Genetics, Kaiser Permanente, Portland, Oregon.
authors.forename: Dana
authors.initials: D
authors.lastname: Kostiner
authors.affiliation: Department of Medical Genetics, Children's National Medical Center, Washington DC.
authors.forename: Dina J
authors.initials: DJ
authors.lastname: Zand
authors.affiliation: Department of Genetics, University of Florida, Gainesville, Florida.
authors.forename: Heather
authors.initials: H
authors.lastname: Stalker
authors.affiliation: Department of Genetics, University of Florida, Gainesville, Florida.
authors.forename: Daniel J
authors.initials: DJ
authors.lastname: Driscoll
authors.affiliation: Department of Human Genetics, Children's Hospital of Orange County, Orange, California.
authors.forename: Taosheng
authors.initials: T
authors.lastname: Huang
authors.affiliation: Signature Genomic Laboratories, Perkin Elmer, Inc., Spokane, Washington.
authors.forename: Jill A
authors.initials: JA
authors.lastname: Rosenfeld
authors.affiliation: Department of Genetics, Kaiser Permanente, San Jose, California.
authors.forename: Xu
authors.initials: X
authors.lastname: Li
authors.affiliation: Department of Medical Genetics, Kaiser Permanente, San Francisco, California.|Department of Genetics, Kaiser Permanente, San Jose, California.
authors.forename: Emily
authors.initials: E
authors.lastname: Chen
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D002648:Child; D058674:Chromosome Duplication; D002874:Chromosome Mapping; D041321:Chromosomes, Human, X; D055028:Comparative Genomic Hybridization; D019066:Facies; D005260:Female; D056726:Genetic Association Studies; D005838:Genotype; D006801:Humans; D008297:Male; D008875:Middle Aged; D010375:Pedigree; D010641:Phenotype; D025064:Sex Chromosome Disorders / Q000175:diagnosis* / Q000235:genetics*; D055815:Young Adult
keywords: DGKK; HUWE1; SHROOM4; Xp11.22 duplication; comparative genomic hybridization; intellectual disability