Research
Print page Print page
Switch language
The Capital Region of Denmark - a part of Copenhagen University Hospital
Published

X-linked congenital ptosis and associated intellectual disability, short stature, microcephaly, cleft palate, digital and genital abnormalities define novel Xq25q26 duplication syndrome

Research output: Contribution to journalJournal articleResearchpeer-review

  1. The CAPOS mutation in ATP1A3 alters Na/K-ATPase function and results in auditory neuropathy which has implications for management

    Research output: Contribution to journalJournal articleResearchpeer-review

  2. Genetic screening of the FLCN gene identify six novel variants and a Danish founder mutation

    Research output: Contribution to journalJournal articleResearchpeer-review

  3. Assessing the genetic architecture of epithelial ovarian cancer histological subtypes

    Research output: Contribution to journalJournal articleResearchpeer-review

  4. Phenotypic subregions within the split-hand/foot malformation 1 locus

    Research output: Contribution to journalJournal articleResearchpeer-review

  1. Age-related renal function decline in Fabry disease patients on enzyme replacement therapy: a longitudinal cohort study

    Research output: Contribution to journalJournal articleResearchpeer-review

  2. Impaired Fat Oxidation During Exercise in Long-Chain Acyl-CoA Dehydrogenase Deficiency Patients and Effect of IV-Glucose

    Research output: Contribution to journalJournal articleResearchpeer-review

  3. Development, behaviour and autism in individuals with SMC1A variants

    Research output: Contribution to journalJournal articleResearchpeer-review

  • R S Møller
  • L R Jensen
  • S M Maas
  • J Filmus
  • M Capurro
  • C Hansen
  • C L M Marcelis
  • K Ravn
  • J Andrieux
  • M Mathieu
  • Eva Maria Kirchhoff
  • O K Rødningen
  • N de Leeuw
  • H G Yntema
  • G Froyen
  • J Vandewalle
  • K Ballon
  • E Klopocki
  • S Joss
  • J Tolmie
  • A C Knegt
  • A M Lund
  • Helle Hjalgrim
  • A W Kuss
  • Nanna Maj Tommerup
  • R Ullmann
  • A P M de Brouwer
  • Petter Strømme
  • Susanne Kjærgaard
  • Zeynep Tümer
  • T Kleefstra
View graph of relations
Submicroscopic duplications along the long arm of the X-chromosome with known phenotypic consequences are relatively rare events. The clinical features resulting from such duplications are various, though they often include intellectual disability, microcephaly, short stature, hypotonia, hypogonadism and feeding difficulties. Female carriers are often phenotypically normal or show a similar but milder phenotype, as in most cases the X-chromosome harbouring the duplication is subject to inactivation. Xq28, which includes MECP2 is the major locus for submicroscopic X-chromosome duplications, whereas duplications in Xq25 and Xq26 have been reported in only a few cases. Using genome-wide array platforms we identified overlapping interstitial Xq25q26 duplications ranging from 0.2 to 4.76 Mb in eight unrelated families with in total five affected males and seven affected females. All affected males shared a common phenotype with intrauterine- and postnatal growth retardation and feeding difficulties in childhood. Three had microcephaly and two out of five suffered from epilepsy. In addition, three males had a distinct facial appearance with congenital bilateral ptosis and large protruding ears and two of them showed a cleft palate. The affected females had various clinical symptoms similar to that of the males with congenital bilateral ptosis in three families as most remarkable feature. Comparison of the gene content of the individual duplications with the respective phenotypes suggested three critical regions with candidate genes (AIFM1, RAB33A, GPC3 and IGSF1) for the common phenotypes, including candidate loci for congenital bilateral ptosis, small head circumference, short stature, genital and digital defects.
Original languageEnglish
JournalHuman Genetics
Volume133
Issue number5
Pages (from-to)625-638
ISSN0340-6717
DOIs
Publication statusPublished - 2014

ID: 42455314