Somatic/gonadal mosaicism for structural autosomal rearrangements: female predominance among carriers of gonadal mosaicism for unbalanced rearrangements

Kovaleva, N. V.; Cotter, Philip D.

doi:10.1186/s13039-015-0211-y

Cited by 9 publications

(14 citation statements)

References 106 publications

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“…Balanced Rea (reciprocal translocations and inversions) were not included in the analysis, comprising 51% of the cases in asymptomatic carriers [2]. Of the remaining 203 cases, there were 65 deletions (32%), 39 duplications (19%), 48 rings (24%), 23 unbalanced translocations (11%), and 28 other Reas (14%).…”

Section: Resultsmentioning

confidence: 99%

“…A recent study of patients with somatic/gonadal mosaicism described differences in cytogenetic profile among asymptomatic and affected individuals [2]. In addition, the study revealed a strong female prevalence among both affected and asymptomatic carriers of somatic/gonadal mosaicism for unbalanced Rea, unlike the typical male prevalence among carriers of balanced Rea.…”

Section: Introductionmentioning

confidence: 98%

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Mosaicism for structural non-centromeric autosomal rearrangements in disease-defined carriers: sex differences in the rearrangements profile and maternal age distributions

Kovaleva¹,

Cotter

2017

Mol Cytogenet

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BackgroundMosaicism for an autosomal structural rearrangement (Rea) associated with clinical manifestation of chromosomal imbalance is rare. Consequently, there is a lack of basic epidemiological characterization of this kind of mosaicism, such as population rate, cytogenetic profile of Reas involved, maternal age distribution, and sex (male to female) ratio among Rea carriers. The objectives of the present study were: (i) determination of the Rea profile in clinically affected individuals, (ii) comparative analysis of the cytogenetic profile and involvement of single chromosomes to rearrangements in affected and previously reported asymptomatic carriers, (iii) analysis of the male/female ratio in carriers of various types of Rea, and, (iv) examination of parental ages distributions according to carriers’ sex.ResultsTwo hundred and forty six disease-defined cases of mosaicism for autosomal non-centromeric Rea with a normal cell line of known sex were identified from the literature. There was a significant difference in single chromosome involvements compared to structural rearrangements between affected and asymptomatic carriers of unbalanced Rea, p =0.0030. In affected carriers, chromosome 18 was most frequently involved in structural rearrangements (12.6% of 246 instances). The least frequently rearranged were chromosomes 16 and 21 (0.8% and 1.2%, respectively). In asymptomatic carriers, the most frequently rearranged were chromosomes 5 and 21 (13% of 51 instances each). Among carriers of “loss” or “gain/loss” of genomic material, a female predominance was observed (50 M/89 F, different from population ratio of 1.06 at p = 0.0002). Carriers of either “gain” or balanced Rea demonstrated typical male predominance (41 M/30 F and 18 M/16 F), not different from 1.06. Maternal and paternal ages were reported in 129 and in 109 cases, respectively. There was a significant difference in maternal age distribution between male and female carriers, with mean maternal age of 25.2 years vs 28.3 years (p = 0.032). However, there was no difference in paternal age, with mean paternal age of 29.4 in both groups.ConclusionThe data suggested that structural rearrangements of certain chromosomes involved in mosaicism may not be tolerated by the embryo, while others have higher survival prospects. Maternal age appears to be a risk factor for somatic mosaicism of structural Rea in female offspring or might cause an adverse effect on male embryo viability.Electronic supplementary materialThe online version of this article (doi:10.1186/s13039-017-0321-9) contains supplementary material, which is available to authorized users.

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Section: Resultsmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 98%

Mosaicism for structural non-centromeric autosomal rearrangements in disease-defined carriers: sex differences in the rearrangements profile and maternal age distributions

Kovaleva¹,

Cotter

2017

Mol Cytogenet

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“…Mosaicism for structural chromosomal rearrangements is extremely rare, detected in 0.002/1,000 patients with reproductive failure [Kovaleva and Cotter, 2016]. Asymptomatic carriers of non-centromeric rearrangements with affected children were evaluated in a study, and among them 33 of 42 were found to be mosaic for an unbalanced rearrangement including 16 ring chromosomes, 8 duplications, 4 unbalanced translocations, and 5 other rearrangements [Kovaleva and Cotter, 2016]. It has also been reported that the prevalence of asymptomatic carriers of an unbalanced rearrangement is more common in females due to male-specific selection against abnormal cells [Kovaleva and Cotter, 2016].…”

Section: Discussionmentioning

confidence: 99%

“…Asymptomatic carriers of non-centromeric rearrangements with affected children were evaluated in a study, and among them 33 of 42 were found to be mosaic for an unbalanced rearrangement including 16 ring chromosomes, 8 duplications, 4 unbalanced translocations, and 5 other rearrangements [Kovaleva and Cotter, 2016]. It has also been reported that the prevalence of asymptomatic carriers of an unbalanced rearrangement is more common in females due to male-specific selection against abnormal cells [Kovaleva and Cotter, 2016]. Gonadal mosaicism in unbalanced chromosome abnormalities is mostly due to postzygotic mutations, but it can also originate during meiosis in trisomic zygotes by 2 parallel trisomic rescue events.…”

Section: Discussionmentioning

confidence: 99%

Three Offspring with Cri-du-Chat Syndrome from Phenotypically Normal Parents

2020

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Cri-du-chat syndrome is characterized by facial dysmorphism, intellectual disability, and multiple congenital anomalies. Most cases occur de novo. Here, we report 3 siblings with cri-du-chat syndrome born to healthy parents. The proband was admitted to our clinic at the age of 6.5 years due to severe intellectual disability, facial dysmorphism, and heart defect. His karyotype showed a deletion of chromosome 5p. Microarray analysis revealed a 29-Mb deletion in chromosome 5p and a 4.7-Mb duplication in chromosome 19q. FISH analysis indicated an unbalanced translocation between 5p13.3 and 19q13.4. During follow-up, the second and the third child of the family were born with the same chromosome abnormality. Parental peripheral blood and skin fibroblast karyotypes as well as the FISH results using chromosome 5p- and 19q-specific subtelomeric probes were normal. FISH analysis of the father's sperm detected a 5p deletion in 12.8% of 200 cells, and microarray analysis confirmed the same unbalanced chromosome abnormality in a mosaic pattern. Uncultured peripheral blood and buccal smear of the father were also studied by FISH to exclude low-level mosaicism and in vitro culture effect. This is the first study that provides molecular evidence of paternal gonadal mosaicism of an unbalanced translocation detected in 3 siblings with cri-du-chat syndrome.

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“…Carriers of segmental mosaicism are also rarely found both among prenatal diagnoses [ 4 ] and among patients referred for cytogenetic testing [ 5 ]. In the general population, segmental mosaicism for balanced chromosome rearrangements (balanced translocations and inversions) and unbalanced autosome rearrangements is extremally rare, with calculated frequencies of 0.02 ‰, 0.005 ‰ respectively; segmental mosaicism for unbalanced autosomal rearrangements was reported as 0.002 ‰ [ 6 ].…”

Section: Introductionmentioning

confidence: 99%

Mosaicism for structural non-centromeric autosomal rearrangement in prenatal diagnoses: evidence for sex-specific selection against chromosomal abnormalities

Kovaleva¹,

Cotter

2017

Mol Cytogenet

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BackgroundMosaicism for chromosome rearrangements is common in preimplantation diagnoses, yet is rare in prenatal diagnoses as well as in other groups of patients referred to cytogenetic testing. Consequently, there is a lack of detailed studies on this kind of mosaicism in all groups of patients. Previous reports have identified a deficit of males among asymptomatic carriers of N/unbalanced Rea. Three mechanisms were proposed for explaining this phenomenon, including a high instability in the early female embryonic development, a male-specific selection against abnormal cells in the early embryo development, or a high intrauterine lethality of male carriers. To address these possibilities, we have performed a meta-analysis of male-to-female ratio (sex ratio, SR) in prenatally diagnosed and in spontaneously aborted carriers of mosaic Rea.ResultsOne hundred and twenty one prenatally detected cases of normal cell line/autosome rearrangement mosaicism (N/Rea) with known carriers’ sex were identified from the literature. Carriers of N/unbalanced Rea presented with 38 abnormal and 28 normal/apparently normal outcomes while carriers of N/balanced Rea presented with 24 normal and 3 abnormal outcomes. 58% of carriers of N/unbalanced Rea with an abnormal outcome displayed a high proportion (> 50%) of amniocytes with the abnormality compared to 25% of carriers with normal/apparently normal outcome. More female carriers of N/unbalanced Rea were identified with an abnormal outcome (15 M/23F) in contrast to a notable male predominance (18 M/10F) among those with normal outcome. Additionally, among spontaneously aborted carriers of N/unbalanced Rea, there was a strong female predominance (7 M/23F).ConclusionPrevious reports have identified a deficit of male among asymptomatic carriers of N/unbalanced Rea. The current data suggests a male-specific selection against chromosomal abnormalities.Electronic supplementary materialThe online version of this article (10.1186/s13039-017-0346-0) contains supplementary material, which is available to authorized users.

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Somatic/gonadal mosaicism for structural autosomal rearrangements: female predominance among carriers of gonadal mosaicism for unbalanced rearrangements

Cited by 9 publications

References 106 publications

Mosaicism for structural non-centromeric autosomal rearrangements in disease-defined carriers: sex differences in the rearrangements profile and maternal age distributions

Mosaicism for structural non-centromeric autosomal rearrangements in disease-defined carriers: sex differences in the rearrangements profile and maternal age distributions

Three Offspring with Cri-du-Chat Syndrome from Phenotypically Normal Parents

Mosaicism for structural non-centromeric autosomal rearrangement in prenatal diagnoses: evidence for sex-specific selection against chromosomal abnormalities

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