RETRACTED: Nested Inversion Polymorphisms Predispose Chromosome 22q11.2 to Meiotic Rearrangements

Demaerel, Wolfram; Vergaelen, Elfi; Swillen, Ann; López-Sánchez, Marcos; Pérez-Jurado, Luís A.; Zackai, Elaine H.; Breckpot, Jeroen; Devriendt, Koenraad; Antshel, Kevin M.; Arango, Celso; Armando, Marco; Bassett, Anne S.; Bearden, Carrie E.; Boot, Erik; Bravo-Sanchez, Marta; Breetvelt, Elemi J.; Busa, Tiffany; Butcher, Nancy J.; Campbell, Linda; Carmel, Miri; Chow, Eva W.C.; Crowley, T. Blaine; Cubells, Joseph F.; Cutler, David J.; Digilio, María Cristina; Duijff, Sasja N.; Eliez, Stéphan; Emanuel, Beverly S.; Epstein, Michael P.; Evers, Rens; Garcia-Moya, Luis Fernandez; Fiksinski, Ania; Fraguas, David; Fremont, Wanda; Fritsch, Rosemarie; García‐Miñaúr, Sixto; Golden, Aaron; Gothelf, Doron; Guo, Tingwei; Gur, Ruben C.; Gur, Raquel E.; Heine-Suñer, Damián; Hestand, Matthew S.; Hooper, Stephen R.; Kates, Wendy R.; Kushan, Leila; Laorden-Nieto, Alejandra; Maeder, Johanna; Marino, Bruno; Marshall, Christian; McCabe, Kathryn; McDonald‐McGinn, Donna M.; Michaelovosky, Elena; Morrow, Bernice E.; Moss, Edward; Mullé, Jennifer G.; Murphy, Declan; Murphy, Kieran C.; Murphy, Clodagh; Niarchou, Maria; Ornstein, Claudia; Philip, Nicole; Repetto, Gabriela M.; Schneider, Maude; Shashi, Vandana; Simon, Tony J.; Tassone, Flora; Unolt, Marta; Amelsvoort, Thérèse van; Bree, Marianne Bernadette van den; Duin, Esther van; Vermeesch, Joris; Vicari, Stefano; Vingerhoets, Claudia; Vorstman, Jacob; Warren, Steve T.; Weinberger, Ronnie; Weisman, Omri; Weizman, Abraham; Zhang, Zhengdong; Zwick, Michael E.

doi:10.1016/j.ajhg.2017.09.002

Cited by 6 publications

(11 citation statements)

References 52 publications

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“…Analysis of physical examination findings by race suggests that some common facial features are either less common or more difficult to identify clinically in non-Caucasian patients, potentially hindering diagnosis. Alternative explanations include differences in access to our referral center or possibly population variations in a heritable predisposition to development of 22q11.2 deletions (Demaerel et al, 2017). …”

Section: Discussionmentioning

confidence: 99%

What is new with 22q? An update from the 22q and You Center at the Children's Hospital of Philadelphia

Campbell

Sheppard

Crowley

et al. 2018

American J of Med Genetics Pt A

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114

130

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Background: 22q11.2 deletion syndrome (22q11.2DS) is caused by recurrent, chromosome specific, low copy repeat mediated copy number losses of chromosome 22q11. The Children’s Hospital of Philadelphia has been involved in the clinical care of individuals with what is now known as 22q11.2DS since our initial report of the association with DiGeorge syndrome in 1982. Methods: We reviewed the medical records on our continuously growing longitudinal cohort of 1,421 patients with molecularly confirmed 22q11.2DS from 1992 to 2018. Results: Most individuals are Caucasian and older than eight years old. The median age at diagnosis was 360 days. The majority of patients (85%) had typical LCR22A-LCR22D deletions, and only 7% of these typical deletions were inherited from a parent harboring the deletion constitutionally. However, 6% of individuals harbored other nested deletions that would not be identified by traditional 22q11.2 FISH, thus requiring an orthogonal technology to diagnose. Major medical problems included immune dysfunction or allergies (77%), palatal abnormalities (67%), congenital heart disease (64%), gastrointestinal difficulties (65%), endocrine dysfunction (>50%), scoliosis (50%), renal anomalies (16%), and airway abnormalities. Median full-scale IQ was 76, with no significant difference between individuals with and without congenital heart disease or hypocalcemia. Characteristic dysmorphic facial features were present in most, but dermatoglyphic patterns of our cohort are similar to normal controls. Conclusions: This is the largest longitudinal study of patients with 22q11.2DS, helping to further describe the condition and aid in diagnosis and management. Further surveillance will likely elucidate additional clinically relevant findings as they age.

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Section: Discussionmentioning

confidence: 99%

What is new with 22q? An update from the 22q and You Center at the Children's Hospital of Philadelphia

Campbell

Sheppard

Crowley

et al. 2018

American J of Med Genetics Pt A

Self Cite

114

130

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“…Thus, yet only parentally derived deletions or duplications may be detected, but no structural changes. Even though single studies showed that it is necessary in MMS like Angelman/Prader-Willi [ 13 ] Williams-Beuren [ 14 ] and Sprintzen velocardiofacial syndrome [ 26 ] also to check for potentially, in the offspring disease causing inversions, no systematic studies in other MMSs were undertaken, yet. This gap was closed by the present study using a simple three-color-FISH probe set, as suggested here in Fig.…”

Section: Discussionmentioning

confidence: 99%

Parental origin of deletions and duplications – about the necessity to check for cryptic inversions

et al. 2018

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BackgroundCopy number variants (CNVs) are the genetic bases for microdeletion/ microduplication syndromes (MMSs). Couples with an affected child and desire to have further children are routinely tested for a potential parental origin of a specific CNV either by molecular karyotyping or by two color fluorescence in situ hybridization (FISH), yet. In the latter case a critical region probe (CRP) is combined with a control probe for identification of the chromosome in question. However, CNVs can arise also due to other reasons, like a recombination-event based on a submicroscopic, cryptic inversion in one of the parents.ResultsSeventy-four patients with different MMSs and overall 81 CNVs were studied here by a novel three color FISH approach. The way how three locus-specific probes are selected (one is the CRP and two are flanking it in a distance of 5-10 Mb) enables to detect or exclude two possible parental conditions as origins of the CNV seen in the index: (i) direct parental origin of the CNV (deletion or duplication) or (ii) a parental cryptic inversion. Thus, for overall 51/81 CNVs (63%) a parental origin could be determined. 36/51 (70.5%) inherited the CNV directly from one of the parents, but 15/51 (29.5%) were due to an exclusively by three color FISH detectable parental inversion. A 2:1 ratio of maternal versus paternal inheritance was found. Also almost two times more male than female were among the index patients.ConclusionThe new, here suggested three color FISH approach is suited for more comprehensive parental studies of patients with MMS. The detection rate for parental origin was increased by 140% in this study. Still, for 30/81 cases (37%) no reason for the ‘de novo’ MMS in the affected index patient could be found by the here suggested FISH-probe set.Electronic supplementary materialThe online version of this article (10.1186/s13039-018-0369-1) contains supplementary material, which is available to authorized users.

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“…All FAM230C-related lincRNA genes that display the TBTA sequence and its satellite/Alu/AT-rich signature are in chr 22, in or near the 22q11.2 deletion region (coordinates chr22:18,820,303–21,489,474) [ 31 ]. Seven genes are within one of the low copy repeats (LCR22A-D) in 22q11.2 (LCR22A-D span coordinates chr22:18,150,000–21,750,000) [ 32 ] ( Fig 3 ). The eighth gene, AP000345.1 (LINC01658) is in LCR22F (formally, LCR22-6’, chr22:23306926–23679116.)…”

Section: Resultsmentioning

confidence: 99%

“… 22q11.2 coordinates are from Guna et al [ 31 ] and LCR22A-D coordinates from Demaerel et al [ 32 ]. Line drawings that represent chromosomal distances, LCR22 positions and lincRNA gene positions are approximate.…”

Section: Resultsmentioning

confidence: 99%

“…Table 4 shows the eight genes that have a high similarity with the 3’ segment of FAM230C and harbor the TBTA-AT-rich sequences. Gene lengths, nt positions analogous to FAM230C positions and gene locations in low copy repeats (LCR22A-D and LCR22F) [ 19 , 20 , 29 , 32 ] in 22q11.2 are shown. Chromosomal coordinates for these genes are from Homo sapiens chromosome 22, GRCh38.p7 Primary Assembly, Sequence ID: NC_000022.11 .…”

Section: Resultsmentioning

confidence: 99%

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A family of long intergenic non-coding RNA genes in human chromosomal region 22q11.2 carry a DNA translocation breakpoint/AT-rich sequence

Delihas

2018

PLoS ONE

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FAM230C, a long intergenic non-coding RNA (lincRNA) gene in human chromosome 13 (chr13) is a member of lincRNA genes termed family with sequence similarity 230. An analysis using bioinformatics search tools and alignment programs was undertaken to determine properties of FAM230C and its related genes. Results reveal that the DNA translocation element, the Translocation Breakpoint Type A (TBTA) sequence, which consists of satellite DNA, Alu elements, and AT-rich sequences is embedded in the FAM230C gene. Eight lincRNA genes related to FAM230C also carry the TBTA sequences. These genes were formed from a large segment of the 3’ half of the FAM230C sequence duplicated in chr22, and are specifically in regions of low copy repeats (LCR22)s, in or close to the 22q.11.2 region. 22q11.2 is a chromosomal segment that undergoes a high rate of DNA translocation and is prone to genetic deletions. FAM230C-related genes present in other chromosomes do not carry the TBTA motif and were formed from the 5’ half region of the FAM230C sequence. These findings identify a high specificity in lincRNA gene formation by gene sequence duplication in different chromosomes.

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RETRACTED: Nested Inversion Polymorphisms Predispose Chromosome 22q11.2 to Meiotic Rearrangements

Cited by 6 publications

References 52 publications

What is new with 22q? An update from the 22q and You Center at the Children's Hospital of Philadelphia

What is new with 22q? An update from the 22q and You Center at the Children's Hospital of Philadelphia

Parental origin of deletions and duplications – about the necessity to check for cryptic inversions

A family of long intergenic non-coding RNA genes in human chromosomal region 22q11.2 carry a DNA translocation breakpoint/AT-rich sequence

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