Homozygosity for a Robertsonian translocation (13q14q) in three offspring of heterozygous parents

Martínez-Castro, Pedro; Ramos, Marcelo de Carvalho; Rey, Juan A.; Benı́tez, Javier; Cascos, A Sánchez

doi:10.1159/000132080

Cited by 19 publications

(14 citation statements)

References 7 publications

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“…A total of nine cases of confirmed RBT homozygosity were identified, involving t(13;14) 19,[24][25][26] and t(14;21). 22,27,28 A further case of t(14;22) homozygosity 29 was also considered with some caveats (Table 1; cases 1-10).…”

Section: Robertsonian Translocationsmentioning

confidence: 99%

“…These include three siblings (cases 1-3) each heterozygous for t (13;14). 19 Exceptions to this included the sole case of unbalanced homozygosity (case 9), that of translocation Down's syndrome, where the parents were unrelated but each heterozygous for t(14;21), 28 and case 7 where only the father was heterozygous, with the second rearrangement arising de novo. 22 For all cases of balanced homozygosity fully reported, ascertainment was following cytogenetic investigation prompted by the presence of an existing RBT within a family member, rather than any specific clinical concern.…”

Section: Robertsonian Translocationsmentioning

confidence: 99%

“…In all such cases, the proband was phenotypically normal. 19,22,24,25,27,29 These include a t(13;14) homozygote identified following an extensive pedigree analysis on a large kindred from an isolated community in Finland (case 4), where data inferred a familial t(13;14) translocation transmitted through nine generations. 24 RBT homozygotes are fertile, as seen in cases 1 and 6, producing one and six children, respectively, with unrelated and karyotypically normal partners.…”

Section: Robertsonian Translocationsmentioning

confidence: 99%

“…Each child, as may be expected was heterozygous for the RBT. 19,24 A third case of successful fertility may include the additional report of homozygosity (case 10) inferred from pedigree studies. 29 This reported a large kindred with a t(14;22) translocation documented over three generations, with an inferred transmission through the previous five, where a male in generation IV was the son of related parents each with inferred carrier status.…”

Section: Robertsonian Translocationsmentioning

confidence: 99%

“…2,8,[16][17][18] Although the familial transmission of such rearrangements across generations is well reported, reports of homozygosity are relatively rare, although include examples of all three forms. [19][20][21] Most data are in the form of individual case reports with description of ascertainment and any associated phenotypic abnormalities, for which great variation exists for individual homozygosities. Of some importance is that homozygosity may be identified during prenatal screening, which may raise clinical and parental concerns regarding the implications of a particular homozygosity.…”

Section: Introductionmentioning

confidence: 99%

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Homozygosity for constitutional chromosomal rearrangements: a systematic review with reference to origin, ascertainment and phenotype

O’Neill¹

2010

J Hum Genet

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Chromosomal translocations and inversions are present in B0.6-1% of individuals. Although the majority are inherited, and the familial transmission across generations is well reported, reports of homozygosity are relatively rare, with most data in the form of individual case reports. A systematic review of all published cases was performed with particular attention to origin, ascertainment and phenotype of the reported homozygosity. A total of 10 cases of Robertsonian translocation (RBT), 6 reciprocal translocation and 19 cases of inversion homozygosity were identified. In RBT homozygosity, the majority of individuals are phenotypically normal, arise from inbreeding within a family that carries a familial translocation, and are ascertained following identification of an existing familial rearrangement rather than any feature specific to the homozygosity. In addition, they are fertile and as expected, their offspring are heterozygous for the translocation. For reciprocal translocations, homozygosity arises in individuals born to related parents from a family who harbor a unique familial translocation. Ascertainment is following investigation of phenotypic abnormalities resulting from consanguinity per se and/or the unmasking of a specific gene mutation. For chromosomal inversions, homozygosity may originate from either related or non-consanguinous parentage. Although many cases are ascertained because of an associated phenotypic abnormality, a high proportion of cases are of normal phenotype and a direct causal relationship is uncertain. There are fewer reports of both Robertsonian and inversion homozygosity than may be expected from the relative frequencies of each class within the population. Keywords: consanguinity; homozygosity; pericentric inversion; reciprocal translocation; Robertsonian translocation INTRODUCTION Structural chromosomal rearrangements detected under light microscopy fall under three broad categories: Robertsonian translocations (RBTs), reciprocal translocations and chromosomal inversions. 1 Data suggest that such rearrangements are present in B0.6-1% of individuals, with reported differences dependant on the population studied (for example unselected newborns or selected prenatal or population studies) and the level of banding techniques used. [2][3][4][5][6] Additional considerations include the proportion of balanced versus unbalanced abnormalities and origin of the rearrangement; that is whether inherited or de novo. The relative prevalence and the underlying mutations rate vary for each category of rearrangement and for specific types within each category.RBTs include non-homologous translocations and homologous forms, with non-homologous RBTs being far more common. 1 Nonhomologous RBTs are the most common recurrent whole-scale structural chromosomal rearrangement in humans being found in approximately 1 in 1000 live births. 2,5 These arise from whole arm exchanges between the short arms of the acrocentric chromosomes (13-15, 21 and 22) to form a single-metacentric chromosome.

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Section: Robertsonian Translocationsmentioning

confidence: 99%

Section: Robertsonian Translocationsmentioning

confidence: 99%

Section: Robertsonian Translocationsmentioning

confidence: 99%

Section: Robertsonian Translocationsmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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Homozygosity for constitutional chromosomal rearrangements: a systematic review with reference to origin, ascertainment and phenotype

O’Neill¹

2010

J Hum Genet

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Reproductive risk in mating between two translocation carriers: Case report and review of the literature

et al. 1993

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We conducted a study to determine the reproductive risk in a couple who were translocation carriers. This couple, who carried balanced reciprocal translocations, experienced habitual abortions. The wife had a karyotype of 46,XX,t(7;13)(p15.3;q12.3) and the husband of 46,XY,t(1;7)(p11.1;p11.1). Chromosome study of their fourth abortus demonstrated a chimera consisting of two cell lines with a 46,XY and a 46,XX,t(1;7)(p11.1;p11.1)pat, -13, + der(7)t(7;13)(p15.3;q12.3)mat, karyotype. A review of the literature indicates that the risk of having unbalanced live offspring or of spontaneous abortion/stillborns is similar in couples in whom both were translocation carriers and in couples in whom one individual was a translocation carrier. The apparent lack of increased reproductive failure may result from the selective disadvantage of aneusomic gametes at fertilization or very early spontaneous abortions of unbalanced conceptuses.

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Identification of a novel recessive RELN mutation using a homozygous balanced reciprocal translocation

Zaki

Shehab

El‐Aleem

et al. 2007

American J of Med Genetics Pt A

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Two siblings from a consanguineous Egyptian marriage showed an identical phenotype of cortical lissencephaly with cerebellar hypoplasia, severe epilepsy, and mental retardation. Examination of karyotype revealed 46, t(7;12)(q22;p13)mat (7;12)(q22;p13)pat in both affected children, suggesting a homozygous reciprocal balanced translocation. Each healthy parent was a carrier of the balanced translocation in the heterozygous state, suggesting homozygous disruption of a gene involved in brain development. There were early spontaneous abortions in this family, as would be expected from transmission of an unbalanced chromosome. A disruption of RELN at 7q22.1 with absence of encoded protein was identified. This is the first demonstration that such rare homozygous translocations can be used to identify recessive disease gene mutations.

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Homozygosity for a Robertsonian translocation (13q14q) in three offspring of heterozygous parents

Cited by 19 publications

References 7 publications

Homozygosity for constitutional chromosomal rearrangements: a systematic review with reference to origin, ascertainment and phenotype

Homozygosity for constitutional chromosomal rearrangements: a systematic review with reference to origin, ascertainment and phenotype

Reproductive risk in mating between two translocation carriers: Case report and review of the literature

Identification of a novel recessive RELN mutation using a homozygous balanced reciprocal translocation

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