Paternal gonadal mosaicism of NIPBL mutation in a father of siblings with Cornelia de Lange syndrome.
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.
Niu
Dau-Ming
DM
Department of Pediatrics, Taipei Veterans General Hospital, Taipei, Taiwan.
Huang
Jing-Ying
JY
Li
Hsin-Yang
HY
Liu
Kai-Ming
KM
Wang
Shih-Ting
ST
Chen
Yann-Jang
YJ
Udaka
Toru
T
Izumi
Kosuke
K
Kosaki
Kenjiro
K
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
D018797:Cell Cycle Proteins; C487465:NIPBL protein, human; D011506:Proteins