Mechanism of origin in two cases of chimerism

Abstract

Chimerism is defined as the presence in a subject of more than one stable and genetically distinct cell line; cases reported so far include both patients with ambiguous genitalia and healthy subjects. The biological mechanisms, which may give origin to chimeras, are complex, and can be understood by analyzing DNA samples of the patients and their parents using molecular techniques. The objective of this study is to identify the mechanism of origin for the 2 cases we report. The first patient is a phenotipically normal girl with normal (external and internal) genitalia; the second patient had ambiguous genitalia and underwent surgery. DNA was purified from blood samples and, limited to Patient 1, from a sample of biliary cyst. Short tandem repeat polymorphisms were analyzed in order to identify the relative parental contribution to the patients. Molecular analyses carried out on the first patient are not fully informative because of two possible explanations (<i>i.e. </i>parthenogenetic and andrognetic chimera), while in the second case the presence of four alleles at some markers allowed us to identify a tetragametic chimera originnated from the fusion of two distinct embryos. Studies carried on one single tissue may not always be conclusive as they do not allow the precise identification of the mechanism of origin. In these cases, studies on more tissues are strongly suggested

A dispermic chimerism detected in a Taiwanese potential unrelated hematopoietic stem cell donor

“…1 HLA typing were performed using saliva and blood samples. 2 HLA typing were performed using saliva, nail and blood samples.…”

“…Chimerism is suspected when individuals have abnormalities in blood typing results, ambiguous genitalia, or abnormal karyotypes. [1][2][3][4][5][6] True chimeras have varying degrees of cell duality in different body tissues. 7 Chimerism can be divided into partial hematopoietic chimerism and wholebody chimerism.…”

Biparental/androgenetic mosaicism in a male with features of overgrowth and placental mesenchymal dysplasia

“…Several mechanisms have been proposed to explain the origin of biparental/androgenetic mosaicism in humans including fusion of a normal zygote and an empty oocyte fertilized by an X‐carrying spermatozoon and undergoing endomitosis, cell division of a tri‐pronuclear zygote leading to a diploid and a haploid cell and consequent replication of a haploid genome, or fusion of a fertilized polar body with a diploid blastomere . Most recently, haplotyping and copy number analysis of single cells suggest spontaneous segregation of the entire parental genome into distinct cell lineages in the first cleavage division …”

“…Isolated clinical features associated with patUPD6, patUPD14, patUPD15, or patUPD20 are described in a very small number of cases but were not observed in our patient. 11 Several mechanisms have been proposed to explain the origin of biparental/androgenetic mosaicism in humans including fusion of a normal zygote and an empty oocyte fertilized by an X-carrying spermatozoon and undergoing endomitosis, 8 cell division of a tri-pronuclear zygote leading to a diploid and a haploid cell and consequent replication of a haploid genome, 5,12 or fusion of a fertilized polar body with a diploid blastomere. 13 Figure S1).…”

Clinical and Genetic Analysis of an Infertile Male with 46,XX/46,XY Chimerism

“…Chimerism refers to the co‐existence of two or more genetically distinct cells come from different zygotes within the same individual and is a rare genetic disorder in humans, although it is common in animals (Tippett, ), whereas mosaicism is formed by different cells as a result of post‐conceptional mitotic errors in a single zygote (Binkhorst, de Leeuw, & Otten, ). To identify the origin of these cells, molecular analyses using informative polymorphic markers and comparisons of the genetic profiles of the patient and the parents can be performed (Minelli et al, ).…”