Isochromosomes 12p and 9p: parental origin and possible mechanisms of formation

Abstract

In a recent study Bugge et al 1 and Kotzot et al 2 reported that isochromosomes 18p originate mainly from maternal meiosis II nondisjunction, followed by misdivision. In order to determine if there is a common mechanism for isochromosome formation, three cases with mosaicism for an additional isochromosome 12p and three cases with tetrasomy 9p were studied. Two probands with isochromosomes 12p and the three cases with isochromosome 9p showed 3 alleles (two different maternal alleles and one paternal allele) at several loci mapping to distal 12p and 9p, respectively. Maternal heterozygosity for distal markers was reduced to homozygosity for markers closer to the centromere in both i(12p) cases and in one i(9p) case. For one patient with isochromosome 12p, the maternal band was clearly stronger than the paternal one at some loci, but two distinct maternal alleles were never seen. For one foetus and the patient with tetrasomy 9p, distal markers showed maternal heterozygosity. All proximal markers were not informative in these two i(9p) cases. Our findings indicate common features in different autosomal isochromosomes: the origin of the isochromosomes analysed is predominantly maternal; and a common mechanism appears to underlie their formation, namely due to meiosis II nondisjunction followed by a rearrangements leading to duplication of the short and loss of the long arm.

Partial tetrasomy 12pter-12p12.3 in a girl with Pallister-Killian syndrome: extraordinary finding of an analphoid, inverted duplicated marker

“…A`Utype' exchange can also be generated by a simple abnormal event in DNA replication, as suggested by Sjo Èsted et al 15 Conversely, isochromosomes of the complete chromosome 12p as well as other short arm isochromosomes mainly originate from maternal meiosis II errors followed by rearrangements leading to duplication of the short and loss of the long arm. 16,17 In conclusion, the case presented here allows to narrow down the PKS critical region to 12pter-12p12.3. Furthermore, it is the first case with proven analphoid marker of chromosome 12p.…”

Paternal meiotic origin of der(21;21)(q10;q10) mosaicism [46,XX/46,XX,der(21;21)(q10;q10),+21] in a girl with mild Down syndrome

“…Moreover, the cascade of meiotic and subsequent postmeiotic errors resembles those leading to an additional isochromosome 9p, 12p, or 18p subsequent to trisomy 9, 12, or 18, respectively, formed at meiosis II [24][25][26] and a combination of partial trisomy 16p and maternal UPD 16 in one case. 21 In conclusion, a minimum of three events is necessary to explain the karyotype in our patient.…”

Congenital diaphragmatic hernia in a patient with tetrasomy 9p

“…Isochromosomes predominantly originate through maternal meiosis type II nondisjunction, followed by a rearrangement or centromeric misdivision, leading to duplication of the short arm and loss of the long arm [8]. Isochromosomes derived from chromosome 9 have been reported and may be grouped in 3 types: isochromosomes with a breakpoint at p10 with no portion of the long arm, isochromosomes with a small amount of the heterochromic region of 9q extending to 9q12 or 9q13, and isochromosomes with a large portion of the long arm of chromosome 9 extending to 9q21 or q22 [9].…”

“…A number of cases were diagnosed prenatally, and the most common ultrasound findings are intrauterine growth restriction, ventriculomegaly, cleft lip/palate, and genitourinary or renal anomaly. As this pattern is suggestive of trisomy 13, chorionic villus sampling or amniocentesis is necessary to make the prenatal diagnosis of tetrasomy 9p [8]. At birth, the phenotype of tetrasomy 9p is usually immediately recognizable because of characteristic craniofacial appearance with hypertelorism/telecanthus, cleft palate/lip, ear malformation/malposition, bulbous/beaked nose, microgna- thia, large mouth with down-turned corners, epicanthal folds, brachycephaly/microcephaly/hydrocephaly, wide sutures/ large fontanels, short neck/excess nuchal skin, and microphthalmia/enophthalmia.…”