X-linked transposition of the great arteries and incomplete penetrance among males with a nonsense mutation in ZIC3

• Published in: European journal of human genetics : EJHG Vol. 8; no. 9; pp. 704 - 708
• Main Authors: Mégarbané, A, Salem, N, Stephan, E, Ashoush, R, Lenoir, D, Delague, V, Kassab, R, Loiselet, J, Bouvagnet, P
• Format: Journal Article
• Language: English
• Published: England Nature Publishing Group 01.09.2000
• Subjects: Alternative Splicing - genetics; Amino Acid Sequence; Arteries; Birth weight; Chromosomes; Codon, Nonsense - genetics; Congenital diseases; Coronary vessels; Defects; DNA Mutational Analysis; Genes; Genetic Linkage; Genetics; Heart; Homeodomain Proteins - genetics; Humans; Infant; Infant, Newborn; Male; Molecular Sequence Data; Mutation; Nonsense mutation; Patients; Pedigree; Penetrance; Point Mutation; Pulmonary arteries; Sex Factors; Transcription Factors - deficiency; Transcription Factors - genetics; Transposition; Transposition of Great Vessels - diagnosis; Transposition of Great Vessels - genetics; Transposition of Great Vessels - mortality; Ultrasonic imaging; Veins & arteries; X Chromosome - genetics; Zinc Fingers - genetics; France; Beirut Lebanon
• DOI: 10.1038/sj.ejhg.5200526
• ISSN: 1018-4813

We report on a Lebanese family in which two maternal cousins suffered and died very early in life from cardiac malformations. Both presented with a transposition of the great arteries associated with one or several other cardiac defects. Various minor midline defects were also observed, but there were no situs abnormalities other than a persistent left superior vena cava in one. A maternal uncle of these two babies was born cyanotic and died on the third post-natal day. Analysis of the ZIC3 gene, revealed the presence of a mutation in the second exon leading to a truncation of the protein. Surprisingly, another maternal uncle of the two affected cousins also had the mutation but was not clinically affected. To our knowledge, this is the first instance of incomplete penetrance in a male for a mutation in a chromosome X gene.