Paternal gonadal mosaicism of NIPBL mutation in a father of siblings with Cornelia de Lange syndrome

Objectives 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‐per...

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Bibliographic Details
Published in:Prenatal diagnosis 2006-11, Vol.26 (11), p.1054-1057
Main Authors: Niu, Dau‐Ming, Huang, Jing‐Ying, Li, Hsin‐Yang, Liu, Kai‐Ming, Wang, Shih‐Ting, Chen, Yann‐Jang, Udaka, Toru, Izumi, Kosuke, Kosaki, Kenjiro
Format: Article
Language:English
Subjects:
Biological and medical sciences
Cornelia de Lange syndrome
De Lange Syndrome - genetics
Fatal Outcome
Fathers
Female
genetic counselling
gonadal mosaicism
Gonads
Gynecology. Andrology. Obstetrics
Humans
Infant, Newborn
Male
Malformations of the nervous system
Management. Prenatal diagnosis
Medical sciences
Mosaicism
Mutation, Missense
Neurology
Nipped‐B‐like gene
Pregnancy. Fetus. Placenta
Proteins - genetics
Sequence Analysis, DNA
Siblings
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Summary:Objectives 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. Conclusion 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. Copyright © 2006 John Wiley & Sons, Ltd.
ISSN:0197-3851
1097-0223
DOI:10.1002/pd.1554