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.
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.
Authors: Dinah M Clark; Ilana Sherer; Matthew A Deardorff; Janice L B Byrne; Kathleen M Loomes; Malgorzata J M Nowaczyk; Laird G Jackson; Ian D Krantz Journal: Am J Med Genet A Date: 2012-06-27 Impact factor: 2.802
Authors: Angela L Schwab; Thérèse M F Tuohy; Michelle Condie; Deborah W Neklason; Randall W Burt Journal: Fam Cancer Date: 2007-11-18 Impact factor: 2.375
Authors: Feliciano J Ramos; Beatriz Puisac; Carolina Baquero-Montoya; Ma Concepción Gil-Rodríguez; Inés Bueno; Matthew A Deardorff; Raoul C Hennekam; Frank J Kaiser; Ian D Krantz; Antonio Musio; Angelo Selicorni; David R FitzPatrick; Juan Pié Journal: Eur J Hum Genet Date: 2014-12-24 Impact factor: 4.246
Authors: Marta Gil-Salvador; Ana Latorre-Pellicer; Cristina Lucia-Campos; María Arnedo; María Teresa Darnaude; Aránzazu Díaz de Bustamante; Rebeca Villares; Carmen Palma Milla; Beatriz Puisac; Antonio Musio; Feliciano J Ramos; Juan Pié Journal: Front Genet Date: 2022-09-28 Impact factor: 4.772