Interchromosomal insertion (11;2): analysis of segregation in 4 generation of the family and characterization of segmental monoand trisomy phenotype in offspring

Interchromosomal insertion is a rare balanced chromosomal rearrangement that occur when an interstitial segment of one chromosome is translocated into another non-homologous chromosome. Carriers of insertions display normal phenotype and fertility, but have an increased risks of spontaneous abortions (SA) and viable offspring with inherited chromosomal imbalance. The aim of study: to assess the interchromosomal ins(11;2)(q21;q31.1q32.3) segregation to determine the genetic risk of inheriting an unbalanced karyotype by the outcome; to analyze segmental mono- and trisomy 2q31.1q32.3 phenotypic manifestations.Family with reproductive failure history was investigated using a clinical, genealogical, ultrasound, cytogenetical (GTG-banding) and morphological methods. Risks of reproductive loss and aneusomic offspring birth were calculated. The outcome prognosis and prenatal diagnostics results were discussed. Clinical, cytogenetical and reproductive history data of carriers ins(11;2) (q21;q31.1q32.3) were presented. The size of insertional segment is about 0,8-0,9% haploid autosomal length (HAL). Outcomes of 15 pregnancies of 6 carriers were as follows: rate of miscarries - 20%, one miscarriage - fetus with karyotype 46,XY, 3 cases - chromosomal imbalance. The segregation ratio for normal:balanced:der(2):der(11) is 3:6:1:1; the empirical risk for forming aneuploid zygotes is 18% (2/11). Segmental monosomy 2q31.1q32.1 phenotypic features in 2 presented patients are similar with clinical signs of 18 previously reported live-born children with monosomy 2q31q33. Ectrodactyly in 2 our patients confirms association of malformation with 2q31.1 region loss. The presented and reported cases data illustrate a possibility of giving birth of offspring with segmental monosomy as well as trisomy 2q31q32, risk of viable offspring with inherited imbalance may be estimated as 30-40%, spontaneous abortions rate - 20-33%. Fetus with trisomy 2q31.1q32.3 showed unspecific signs of autosomal imbalance. Pattern of phenotypical features reported in 2 relatives with der(2)ins(11;2) correlates with clinically recognizable monosomy 2q31q32 syndrome. Microcephaly, cleft palate/cleft lip and palate, ectrodactyly are the main diagnostic markers of fetal pathology which can be identified using prenatal ultrasound investigation.

interchromosomal insertion, derivative chromosome, segmental monosomy, segmental trisomy, genetic risk, genetic counseling

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