title: Mosaicism for c.431_454dup in ARX causes a mild Partington syndrome phenotype.
abstract: A common in frame duplication in ARX (c.431_454dup24) was found in a five year-old boy who presented with mild Partington syndrome. The duplication was detected by PCR amplification followed by fragment length analysis and was located in exon 2 spanning the two polyalanine tracts commonly seen to expand. Detection of the duplication by DNA sequencing was difficult due to preferential sequencing of the normal allele, demonstrating the superiority of fragment length analysis in mosaic cases. The clinical symptoms were mild to moderate developmental delay with only the hand dystonia to suggest Partington syndrome. This patient is the first male reported to be mosaic for the duplication, and his clinical features are subtle. This study shows that in males with a phenotype of mild Partington syndrome and in heterozygous females fragment length analysis should be preferred over DNA sequencing.
authors.affiliation: Applied Human Molecular Genetics, Kennedy Center, Rigshospitalet, University of Copenhagen, DK-2600 Glostrup, Denmark; Department of Cellular and Molecular Medicine, University of Copenhagen, DK-2200 Copenhagen, Denmark. Electronic address: Karen.groenskov@regionh.dk.
authors.forename: Karen
authors.initials: K
authors.lastname: Grønskov
authors.affiliation: Genetic Counseling Clinic, Kennedy Center, Rigshospitalet, University of Copenhagen, DK-2600 Glostrup, Denmark.
authors.forename: Birgitte
authors.initials: B
authors.lastname: Diness
authors.affiliation: Center for Rett Syndrome, Kennedy Center, Rigshospitalet, University of Copenhagen, DK-2600 Glostrup, Denmark.
authors.forename: Michelle
authors.initials: M
authors.lastname: Stahlhut
authors.affiliation: Department of Pediatrics, Næstved Hospital, DK-4700 Næstved, Denmark.
authors.forename: Monica
authors.initials: M
authors.lastname: Zilmer
authors.affiliation: Applied Human Molecular Genetics, Kennedy Center, Rigshospitalet, University of Copenhagen, DK-2600 Glostrup, Denmark.
authors.forename: Zeynep
authors.initials: Z
authors.lastname: Tümer
authors.affiliation: Center for Rett Syndrome, Kennedy Center, Rigshospitalet, University of Copenhagen, DK-2600 Glostrup, Denmark.
authors.forename: Anne-Marie
authors.initials: AM
authors.lastname: Bisgaard
authors.affiliation: Applied Human Molecular Genetics, Kennedy Center, Rigshospitalet, University of Copenhagen, DK-2600 Glostrup, Denmark.
authors.forename: Karen
authors.initials: K
authors.lastname: Brøndum-Nielsen
mesh_terms: D001259:Ataxia / Q000235:genetics* / Q000473:pathology; D001483:Base Sequence; D002675:Child, Preschool; D004252:DNA Mutational Analysis; D020440:Gene Duplication; D018398:Homeodomain Proteins / Q000235:genetics*; D006801:Humans; D008297:Male; D038901:X-Linked Intellectual Disability / Q000235:genetics* / Q000473:pathology; D009030:Mosaicism; D010641:Phenotype; D012640:Seizures / Q000235:genetics* / Q000473:pathology; D014157:Transcription Factors / Q000235:genetics*
chemical_list: C469264:ARX protein, human; D018398:Homeodomain Proteins; D014157:Transcription Factors
keywords: ARX; DNA sequencing; Duplication; Mosaicism; PCR fragment length analysis; Partington syndrome