title: Paternal gonadal mosaicism of NIPBL mutation in a father of siblings with Cornelia de Lange syndrome.
abstract: OBJECTIVE
  We report two siblings, a boy and a girl, with Cornelia de Lange syndrome (CdLS), born to unaffected parents, and attempt to delineate the underlying molecular mechanism leading to familial recurrence.
  
  
  METHODS
  Nipped-B-like (NIPBL) gene mutations were screened using in denaturing high-performance liquid chromatography and sequencing in peripheral blood samples, from one of the affected siblings and her parents, as well as from a sperm sample from the father.
  
  
  RESULTS
  A heterozygous missense NIPBL mutation, D2433G, was identified in the peripheral blood sample of the affected girl, but not in the peripheral blood samples of her parents. The D2433G mutation was also found in the sperm sample of the father.
  
  
  CONCLUSIONS
  Gonadal mosaicism represents an underappreciated feature of the inheritance pattern of CdLS. To our knowledge, the girl represents the first CdLS patient whose father was documented to have a population of mutant sperm. When a sperm analysis indicates the presence of a mutant allele, it may be reasonable to offer prenatal genetic testing to the family in subsequent pregnancies, given that the sensitivity of fetal ultrasonography is relatively low.
authors.affiliation: Department of Pediatrics, Taipei Veterans General Hospital, Taipei, Taiwan.
authors.forename: Dau-Ming
authors.initials: DM
authors.lastname: Niu
authors.forename: Jing-Ying
authors.initials: JY
authors.lastname: Huang
authors.forename: Hsin-Yang
authors.initials: HY
authors.lastname: Li
authors.forename: Kai-Ming
authors.initials: KM
authors.lastname: Liu
authors.forename: Shih-Ting
authors.initials: ST
authors.lastname: Wang
authors.forename: Yann-Jang
authors.initials: YJ
authors.lastname: Chen
authors.forename: Toru
authors.initials: T
authors.lastname: Udaka
authors.forename: Kosuke
authors.initials: K
authors.lastname: Izumi
authors.forename: Kenjiro
authors.initials: K
authors.lastname: Kosaki
mesh_terms: D018797:Cell Cycle Proteins; D003635:De Lange Syndrome / Q000235:genetics*; D017809:Fatal Outcome; D005220:Fathers; D005260:Female; D006066:Gonads; D006801:Humans; D007231:Infant, Newborn; D008297:Male; D009030:Mosaicism; D020125:Mutation, Missense; D011506:Proteins / Q000235:genetics*; D017422:Sequence Analysis, DNA; D035781:Siblings
chemical_list: D018797:Cell Cycle Proteins; C487465:NIPBL protein, human; D011506:Proteins