Two cases of mosaic RhD blood-group phenotypes and paternal isodisomy for chromosome 1

Abstract

We encountered a 22-year-old man (case 1) and a 23-year-old woman (case 2), both unrelated and healthy. They were mosaic for the Rh blood group phenotype: one erythrocyte population was D-positive and the other was D-negative. Flow cytometric analysis of density profile of RhD antigen in their erythrocytes, and cytogenetic analysis including in situ hybridization using an RHD/RHCE-containing PAC clone, excluded a deletion of the RHD/RHCE gene complex, but suggested the presence of cells with uniparental disomy for chromosome 1 (UPD1). Microsatellite marker analysis was performed in both probands and their family members. In case 1, the analysis with markers spanning the chromosome 1 revealed both maternal and paternal alleles in his peripheral blood leukocytes (PBL), Epstein-Barr virus-transformed lymphoblastoid cells (EBL), and buccal mucosal cells. However, only paternal alleles were detected in all of 50 individual pieces of his hair or hair-roots and all of five monoclonal cell lines cloned from his established EBL. There was no direct evidence of heterozygous, biparental alleles in these two tissues. The presence of maternal isodisomy 1 was not absolutely ruled out in other tissues examined in case 1. Similar results were obtained in case 2, showing biparental, disomic patterns in her PBL and in 15 of 20 pieces of her hair roots, and showing monoallelic patterns in the remaining five pieces of hair roots. Analysis with markers for other autosomes confirmed their biparental inheritance. These findings indicated that both cases had at least two cell populations, one population having paternal UPD1 (isodisomy 1), and another heterozygous, biparental disomy 1. We emphasize that isodisomy for chromosome 1 is not infrequent and may cause unusual RhD phenotype, as seen in cases we described.

Uniparental isodisomy of chromosome 1 results in glycogen storage disease type III with profound growth retardation

“…All of them were identified through the detection of homozygosity for an autosomal recessive disorder in discordance with the segregation analysis. Other two cases were incidentally identified during genome‐wide linkage analysis (Field, Tobias, Robinson, Paisey, & Bain, ; Miyoshi et al, ) and further two cases have been described with a phenotype that could not be attributed to a known recessive condition (Chen et al, ; Röthlisberger et al, ). Particularly, the karyotype of a female with paternal UPD1 (Chen et al, ) presenting with myopathy, infertility and short stature, showed the presence of two isochromosomes 1, which likely have arisen from an abnormal division following chromosome 1 monosomy.…”

The consequences of uniparental disomy and copy number neutral loss-of-heterozygosity during human development and cancer

“…Recently a number of mosaic genome‐wide pUPDs were described with BWS‐like phenotypes (Morales et al, 2009; Yamazawa et al, 2011; Romanelli et al, 2011b). This is remarkable, since non‐mosaic genome‐wide pUPD is incompatible with fetal development and results in a hydatidiform mole (Devriendt 2005).…”

“…This is remarkable, since non‐mosaic genome‐wide pUPD is incompatible with fetal development and results in a hydatidiform mole (Devriendt 2005). Two of these rare BWS‐like cases were also reported to have developed multiple tumours (Morales et al, 2009; Romanelli et al, 2011b). The most likely mechanism of mosaic genome‐wide UPD is normal fertilization, followed by a failure of replication and condensation of the maternal pronuclei, followed by paternal genome endoreduplication, resulting in androgenetic/biparental mosaicism, with over‐representation of genome‐wide pUPD cell lines (Figure 2F).…”

Chediak–Higashi syndrome with early developmental delay resulting from paternal heterodisomy of chromosome 1

“…Since the first case by Pulkkinen et al 1997, at least 19 cases of uniparental hetero‐ or isodisomy of chromosome 1 have been reported resulting in various autosomal recessive conditions with a typical phenotype, suggesting the lack of imprinted genes affecting growth and development on either the paternal or maternal alleles on that chromosome [Pulkkinen et al, 1997; Field et al, 1998; Gelb et al, 1998; Dufourcq‐Lagelouse et al, 1999; Takizawa et al, 2000; Miyoshi et al, 2001; Thompson et al, 2002; Fassihi et al, 2005; Zeng et al, 2006; Riveiro‐Alvarez et al, 2007; Benko et al, 2008] reviewed in a recent report [Turner et al, 2007].…”

“…Maternal isodisomy of chromosome 1 resulting in a homozygous nonsense mutation (c.2620delT, p.Phe874fsX898) in the LYST/CHS1 gene has been previously described in a 6‐year‐old male with classic CHS and normal physical and neurocognitive development [Dufourcq‐Lagelouse et al, 1999]. Additionally, chromosome 1 maternal or paternal iso‐ or heterodisomy has been reported in association with various isolated recessive disorders without other symptoms, such as growth or cognitive delays, suggesting a lack of imprinted genes on chromosome 1 [Pulkkinen et al, 1997; Field et al, 1998; Gelb et al, 1998; Takizawa et al, 2000; Miyoshi et al, 2001; Thompson et al, 2002; Fassihi et al, 2005; Zeng et al, 2006; Riveiro‐Alvarez et al, 2007; Turner et al, 2007; Benko et al, 2008].…”