Autosomal insertional translocation mimicking an X-linked mode of inheritance

• Published in: European journal of medical genetics Vol. 56; no. 1; pp. 46 - 49
• Main Authors: Thierry, Gaelle, Pichon, Olivier, Briand, Annaig, Poulain, Damien, Sznajer, Yves, David, Albert, Le Caignec, Cédric
• Format: Journal Article
• Language: English
• Published: Netherlands Elsevier Masson SAS 01-01-2013
• Subjects: Chromosomes, Human, Pair 6; Chromosomes, Human, Pair 8; Comparative Genomic Hybridization; Deletion; Duplication; Humans; In Situ Hybridization, Fluorescence; Inheritance Patterns; Insertion; Intellectual Disability - diagnosis; Intellectual Disability - genetics; Male; Medical Education; Mental retardation; Mutagenesis, Insertional; Translocation, Genetic; X-linked intellectual disability; ZFPM2; Insertion; Deletion; X-linked intellectual disability; Duplication; ZFPM2; Mental retardation
• ISSN: 1769-7212; 1878-0849
• DOI: 10.1016/j.ejmg.2012.10.006

Abstract Unbalanced insertional translocations are a rare cause of intellectual disability. An unbalanced insertional translocation is a rare chromosomal imbalance, which may result from a balanced insertional translocation present in a phenotypically normal parent. We report here three brothers with intellectual disability, short stature, microcephaly, craniofacial anomalies and small testes. Since their parents and their sister were all phenotypically normal, the pattern of the family suggested an X-linked mode of inheritance. Surprisingly, we identified by array comparative genomic hybridization (aCGH) and fluorescent in situ hybridization (FISH) in the three brothers an 8q22.3q23.2 deletion resulting from a balanced insertional translocation present in their healthy father. The deletion encompassed the ZFPM2 gene known to be involved in gonadal development, which is consistent with the small testes and abnormal endocrine dosages in the affected brothers. The present report also illustrates that parental analyses by aCGH or qPCR methods are not sufficient when a de novo deletion or duplication is identified in an affected child and that FISH analysis should be performed on metaphase spreads in both parents to deliver an accurate genetic counseling.