The Principles of Clinical Cytogenetics - Extra Materials - Springer

524 Jin-Chen Wang
Fig. 3. A diagrammatic representation of maternal UPD formation by “trisomy rescue.” A trisomic zygote
resulting from maternal meiosis I nondisjunction is depicted here. Loss of one of the trisomic chromosomes
through either mitotic nondisjunction or anaphase lag results in euploidy. Uniparental disomy occurs in onethird
of these cases. m 1 and m 2 : maternally derived chromosomes; p: paternally derived chromosome.
which the father was a heterozygote and the mother was normal (154). The child was otherwise
developmentally normal. Three additional patients, one with congenital insensitivity to pain with
anhidrosis, one with Herlitz junctional epidermolysis bulosa, and one with Leber congenital amaurosis,
were recently reported (155–157). All three had paternal isodisomy for chromosome 1. None had
any overt dysmorphisms or malformations. Their phenotype resulted from having two copies of
the mutated recessive genes, both inherited from their fathers. Another patient was a 43-year-old
female with short stature, ptosis, micro/retrognathia, scoliosis, hearing loss, myopathy, and infertility.
She has isochromosomes for the short arm and long arm of chromosome 1 [i(1)(p10),i(1)(q10);
see Chapters 3 and 9] (158). It was not clear whether the abnormal phenotype in this woman resulted
from an imprinting effect or from homozygosity for some undetected recessive alleles. These observations
provide no clear evidence for an imprinting effect of paternal UPD 1.
upd(2)mat
Maternal UPD for chromosome 2 has been reported in at least seven cases. Four cases were associated
with confined placental mosaicism (CPM) for trisomy 2 (159–162), two cases resulted from de
novo isochromosome formation of the short arm and long arm of chromosome 2 [i(2)(p10),i(2)(q10);
see Chapters 3 and 9] (163,164), and one case was discovered at age 3 during paternity testing (165).
In the latter case and one of the cases with isochromosomes, no phenotypic abnormalities were present
(161,165). A common phenotype was observed in the other five cases. This includes intrauterine
growth retardation (IUGR), oligohydramnios, pulmonary hypoplasia, hypospadias (in two patients),
and normal development in the four surviving patients at ages 6 months, 20 months, 31 months, and
8 years, respectively. IUGR, oligohydramnios, and pulmonary hypoplasia can be explained by placental
dysfunction as a result of trisomy 2 mosaicism. However, these same features were also present
in one of the cases with isochromosomes (164), suggesting a possible imprinting effect of maternal
UPD 2. In another case reported recently, UPD for maternal 2q and paternal 2p was detected in a 36year-old
woman with normal physical and mental development (166). Therefore, it is still not clear
whether maternal UPD 2 confers an imprinting effect.