Partial 5p monosomy or trisomy in 11 patients from a family with a t(5;15)(p13.3;p12) translocation

Carvalho, Acácia Fernandes Lacerda de; Bellucco, Fernanda Teixeira da Silva; Kulikowski, Leslie Domenici; Toralles, Maria Betânia Pereira; Melaragno, Maria Isabel

doi:10.1007/s00439-008-0557-x

Cited by 14 publications

(13 citation statements)

References 29 publications

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“…Large deletions and unbalanced translocations in CdCS are associated with severe neurological impairment and higher frequency of congenital malformations [Wilkins et al, 1983;Mainardi et al, 2001]. Patients with large deletions, similar to our patients, were reported to have severe intellectual disability, severe speech delay, behavioral problems, and musculoskeletal involvement [de Carvalho et al, 2008;Santo et al, 2016]. Santo at al.…”

Section: Discussionsupporting

confidence: 73%

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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Section: Discussionsupporting

confidence: 73%

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

2020

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“…The following probes were applied: RP11‐714I4 (chrX:38,470,254–38,631,716), RP11‐34P8 (chrX:73,914,389–74,105,538), RP11‐1072D12 (chr3:95,897,890–96,067,315), CTD‐3225H3 (chrX:29,125,517–29,260,404), RP11‐790H16 (chr19:53,164,395–53,352,424), and RP11‐203K12 (chrX:74,592,669–74,748,513). They were FITC (fluorescein isothiocyanate) or TRITC (tetramethyl rhodamine isothiocyanate) labeled by nick‐translation and hybridized on metaphase spread [de Carvalho et al, ].…”

Section: Methodsmentioning

confidence: 99%

X‐linked intellectual disability related genes disrupted by balanced X‐autosome translocations

Moysés-Oliveira

Guilherme

Meloni

et al. 2015

American J of Med Genetics Pt B

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Detailed molecular characterization of chromosomal rearrangements involving X-chromosome has been a key strategy in identifying X-linked intellectual disability-causing genes. We fine-mapped the breakpoints in four women with balanced X-autosome translocations and variable phenotypes, in order to investigate the corresponding genetic contribution to intellectual disability. We addressed the impact of the gene interruptions in transcription and discussed the consequences of their functional impairment in neurodevelopment. Three patients presented with cognitive impairment, reinforcing the association between the disrupted genes (TSPAN7-MRX58, KIAA2022-MRX98, and IL1RAPL1-MRX21/34) and intellectual disability. While gene expression analysis showed absence of TSPAN7 and KIAA2022 expression in the patients, the unexpected expression of IL1RAPL1 suggested a fusion transcript ZNF611-IL1RAPL1 under the control of the ZNF611 promoter, gene disrupted at the autosomal breakpoint. The X-chromosomal breakpoint definition in the fourth patient, a woman with normal intellectual abilities, revealed disruption of the ZDHHC15 gene (MRX91). The expression assays did not detect ZDHHC15 gene expression in the patient, thus questioning its involvement in intellectual disability. Revealing the disruption of an X-linked intellectual disability-related gene in patients with balanced X-autosome translocation is a useful tool for a better characterization of critical genes in neurodevelopment. © 2015 Wiley Periodicals, Inc.

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“…FISH analyses were performed according to published protocols [27] in order to confirm chromosome abnormalities, STR and array CGH results. A total of twenty-one bacterial artificial chromosome (BAC) clones (RP11-59C22, RP11-810B19, RP11-473F9, RP11-1029M14, RP11-976O8, RP11-125A21, RP11-241M9, RP11-1122G9, RP11-420J19, RP11-23D12, RP11-349J3, RP11-373F8, RP11-1022E23, RP11-100I1, RP11-1055J13, RP11-428C17, RP11-62K5, RP11-106P5, RP11-318A6, RP11-1005N9, and RP11-876N17) mapping to 5p13.3–p15.32 region and three BAC clones (RP11-1029D4, RP11-916H5, and RP11-945C11) mapping to chromosome 21q21.1–q22.11 were selected from the University of California-Santa Cruz (UCSC), with detailed corresponding linear map position available in genome (Table 2).…”

Section: Methodsmentioning

confidence: 99%

A Familial Cri-du-Chat/5p Deletion Syndrome Resulted from Rare Maternal Complex Chromosomal Rearrangements (CCRs) and/or Possible Chromosome 5p Chromothripsis

Jiang

et al. 2013

PLoS ONE

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Cri-du-Chat syndrome (MIM 123450) is a chromosomal syndrome characterized by the characteristic features, including cat-like cry and chromosome 5p deletions. We report a family with five individuals showing chromosomal rearrangements involving 5p, resulting from rare maternal complex chromosomal rearrangements (CCRs), diagnosed post- and pre-natally by comprehensive molecular and cytogenetic analyses. Two probands, including a 4½-year-old brother and his 2½-year- old sister, showed no diagnostic cat cry during infancy, but presented with developmental delay, dysmorphic and autistic features. Both patients had an interstitial deletion del(5)(p13.3p15.33) spanning ∼26.22 Mb. The phenotypically normal mother had de novo CCRs involving 11 breakpoints and three chromosomes: ins(11;5) (q23;p14.1p15.31),ins(21;5)(q21;p13.3p14.1),ins(21;5)(q21;p15.31p15.33),inv(7)(p22q32)dn. In addition to these two children, she had three first-trimester miscarriages, two terminations due to the identification of the 5p deletion and one delivery of a phenotypically normal daughter. The unaffected daughter had the maternal ins(11;5) identified prenatally and an identical maternal allele haplotype of 5p. Array CGH did not detect any copy number changes in the mother, and revealed three interstitial deletions within 5p15.33-p13.3, in the unaffected daughter, likely products of the maternal insertions ins(21;5). Chromothripsis has been recently reported as a mechanism drives germline CCRs in pediatric patients with congenital defects. We postulate that the unique CCRs in the phenotypically normal mother could resulted from chromosome 5p chromothripsis, that further resulted in the interstitial 5p deletions in the unaffected daughter. Further high resolution sequencing based analysis is needed to determine whether chromothripsis is also present as a germline structural variation in phenotypically normal individuals in this family.

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Partial 5p monosomy or trisomy in 11 patients from a family with a t(5;15)(p13.3;p12) translocation

Cited by 14 publications

References 29 publications

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

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

X‐linked intellectual disability related genes disrupted by balanced X‐autosome translocations

A Familial Cri-du-Chat/5p Deletion Syndrome Resulted from Rare Maternal Complex Chromosomal Rearrangements (CCRs) and/or Possible Chromosome 5p Chromothripsis

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