Segregation of a t(1;3) translocation in multiple affected family members with both types of adjacent‐1 segregants

Abstract

A subtle balanced translocation involving the terminal regions of 1q and 3p was identified in a large family by high-resolution karyotype analysis and confirmed by fluorescence in situ hybridization (FISH) analysis. In this family, segregation of a balanced t(1:3)(q42.3;p25) chromosome translocation led to two types of viable unbalanced complements. The proband inherited the derivative chromosome 3, resulting in partial trisomy of 1q and partial monosomy of 3p. A paternal uncle and cousin had the reciprocal rearrangement with a derivative of chromosome 1, resulting in partial monosomy for 1q and partial trisomy for 3p. While profound mental and physical retardation and congenital heart defects were characteristics for both rearrangements, facial dysmorphism was quite distinct for each imbalance. Individuals who had the derivative chromosome 3 had a long face, wide eyebrows, small palpebral fissures, hypertelorism, prominent glabella, a large tip of the nose, long philtrum with thin upper lip, and low set-ears. In contrast, family members with the derivative of chromosome 1 had a tall forehead with bifrontal narrowing, full and large cheeks, and large simple ears. Since the translocated segments are small and approximately equal in size in this family, it is not surprising that viability was seen in individuals with both types of adjacent-1 segregation. In this kindred, the ratio of normal to abnormal individuals born to balanced carriers is believed to be about 1:1.5. This suggests that the recurrence risk for carriers is 50%.

FISH and array‐CGH analysis of a complex chromosome 3 aberration suggests that loss of CNTN4 and CRBN contributes to mental retardation in 3pter deletions

“…Both the 3pÀ syndrome and the trisomy 3p syndrome are recognized causes of malformations and mental retardation. Although in several of the published cases the 3p gain or loss is the result of an unbalanced translocation involving also other chromosomes, unique and shared features of the two syndromes have been described [Narahara et al, 1990;Phipps et al, 1994;Conte et al, 1995;Knight et al, 1995;Chen et al, 1996;Drumheller et al, 1996;Kotzot et al, 1996;Jenderny et al, 1998;Angeloni et al, 1999;Chen et al, 1999;Kennedy et al, 2000;Smeets et al, 2001;Cargile et al, 2002;Endris et al, 2002;Fernandez et al, 2004;Kozma et al, 2004]. A summary of the associated main features, derived from the ''Catalogue of unbalanced chromosome aberrations in man'' by Schinzel [2001] is presented in Table II.…”

Unbalanced Translocations Involving Chromosome Region 10q25.3q26.3 in Patients with Intellectual Disability and Complex Phenotypes

“…If both types of gametes have the same chance of survival, we can expect that in families having several affected children, the number of persons with both types of imbalance will be approximately equal. However, families having children with both types of imbalance occur rarely [Kozma et al, 2004;Palomares et al, 2005;Schmidt et al, 2012], and in the vast majority of families, 2 (or more) affected siblings have the same imbalance.…”

Bayesian Assessment of Genetic Risk in Families with a Balanced Translocation

“…Case 1: 46,XY,t(1;3)(q43;p21) Consider a consultand who is a male heterozygote 46,XY,t(1;3)(q43;p21) with family data (after correction for ascertainment bias) x f am = 7, n f am = 37 (see, e.g., IV-16 in Reiss et al (1986)). Gardner et al (2004), summarizing data in Kozma et al (1983), report that a similar translocation, t(1;3)(q42.3;p25), has an LBR of 7/11 (Table 5-5). This is especially high because both translocated segments were small and there were multiple viable unbalanced rearrangements (Kozma et al 1983;Gardner et al 2004).…”

“…Gardner et al (2004), summarizing data in Kozma et al (1983), report that a similar translocation, t(1;3)(q42.3;p25), has an LBR of 7/11 (Table 5-5). This is especially high because both translocated segments were small and there were multiple viable unbalanced rearrangements (Kozma et al 1983;Gardner et al 2004). By comparison, only the partial trisomy 3p appears to be viable in the consultand's family.…”