Ring chromosome 9 [r(9)(p24q34)]: A report of two cases

Purandare, Smita M.; Lee, Jiyun; Hassed, Susan J.; Steele, Marilyn I.; Blackett, Piers R.; Mulvihill, John J.; Li, Shibo

doi:10.1002/ajmg.a.30382

Cited by 19 publications

(10 citation statements)

References 23 publications

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“…Clinical features of the ring 9 cases described in the literature, including the present case, are comparable to those of the 9pter and 9qter deletion cases [Purandare et al, ; Sheth et al, ]. It should however be taken into consideration that ring chromosomes are likely to have more complex pathology, due to deletion, ring formation, ring stability and mosaicism, compared to pure terminal deletions.…”

Section: Resultssupporting

confidence: 77%

“…Slight, on the left. Data collected from www.nlm.nih.gov/mesh/, www.OMIM.org, Purandare et al [], Hauge et al [], Swinkels et al [].…”

Section: Resultsmentioning

confidence: 99%

“…Ring chromosome 9 [r(9)] is a rare condition and to our knowledge only 27 patients have previously been reported in the literature [Jacobsen et al, ; Fraisse et al, ; Kistenmacher et al, ; Nakajima et al, ; Cavaliere et al, ; Metaxotou‐Stavridaki and Kalpini‐Mavrou, ; Fryns et al, ; Inouye et al, ; Dipierri and Matayoshi, ; Portnoi et al, ; Hess and Meisner, ; Kasa and Kasai, ; Leung and Rudd, ; Manouvrier‐Hanu et al, ; Pfeiffer et al, ; Van Maldergem et al, ; Kontiokari et al, ; Lanzi et al, ; Raymond et al, ; Seghezzi et al, ; Sigurdardottir et al, ; Stumm et al, ; Purandare et al, ; Chen et al, ; Sheth et al, ; Ye et al, ]. The most typical cause of ring formation is a terminal deletion on both p and q arms, creating “sticky ends” which fuse.…”

Section: Introductionmentioning

confidence: 99%

“…The most typical cause of ring formation is a terminal deletion on both p and q arms, creating “sticky ends” which fuse. Most common breakpoints are found between 9p24–p22 and 9q33–q34, but end‐to‐end fusion of palindromic telomere sequences has also been reported [Purandare et al, ]. Ring chromosomes occur in 1/50,000 fetuses and they have been associated with failure to thrive, growth defects and patchy skin pigment changes.…”

Section: Introductionmentioning

confidence: 99%

“…The phenotypes of r(9) patients vary depending on the size and location of the deletions. Common features are developmental delay, facial dysmorphism, microcephaly, genital abnormalities, cardiac malformations, limb and skeletal anomalies, and infectious complications [Purandare et al, ].…”

Section: Introductionmentioning

confidence: 99%

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Ring chromosome 9 in a girl with developmental delay and dysmorphic features: Case report and review of the literature

Sibbesen

Jespersgaard

Alosi

et al. 2013

American J of Med Genetics Pt A

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In this report, we describe a female child with dysmorphic features and developmental delay. Chromosome microarray analysis followed by conventional karyotyping revealed a ring chromosome 9 with a 12 Mb deletion at 9pter-p23 and a 540 kb deletion at 9q34.3-qter. Four percent of the analyzed cells had monosomy 9. The patient has the features of both the Kleefstra syndrome and the chromosome 9p-syndrome, including trigonocephaly, long philtrum, hypertelorism, and retro-/micronagthia. The deletion of the patient overlaps with several of the proposed critical regions for the 9p deletion syndrome.

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Section: Resultssupporting

confidence: 77%

“…Slight, on the left. Data collected from www.nlm.nih.gov/mesh/, www.OMIM.org, Purandare et al [], Hauge et al [], Swinkels et al [].…”

Section: Resultsmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

See 3 more Smart Citations

Ring chromosome 9 in a girl with developmental delay and dysmorphic features: Case report and review of the literature

Sibbesen

Jespersgaard

Alosi

et al. 2013

American J of Med Genetics Pt A

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Ring chromosome formation by intra‐strand repairing of subtelomeric double stand breaks and clinico‐cytogenomic correlations for ring chromosome 9

Chai

Wen

et al. 2020

American J of Med Genetics Pt A

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Constitutional ring chromosome 9, r(9), is a rare chromosomal disorder. Cytogenomic analyses by karyotyping, array comparative genomic hybridization (aCGH) and whole genome sequencing (WGS) were performed in a patient of r(9). Karyotyping detected a mosaic pattern of r(9) and monosomy 9 in 83% and 17% of cells, respectively. aCGH detected subtelomeric deletions of 407 kb at 9p24.3 and 884 kb at 9q34.3 and an interstitial duplication of 5.879 Mb at 9q33.2q34.11. WGS revealed double strand breaks (DSBs) at ends of 9p24.3 and 9q34.3, inverted repeats at ends of subtelomeric and 9q33.2q34.11 regions, and microhomology sequences at the junctions of this r(9). This is the first report of r(9) analyzed by WGS to delineate the mechanism of ring chromosome formation from repairing of subtelomeric DSBs. The loss of telomeres by subtelomeric DSBs triggered inverted repeats induced intra-strand foldback and then microhomology mediated synthesis and ligation, which resulted in the formation of this r(9) with distal deletions and an interstitial duplication. Review of literature found seven patients of r(9) with clinical and cytogenomic findings. These patients and the present patient were registered into the Human Ring Chromosome Registry and a map correlating critical regions and candidate genes with relevant phenotypes was constructed. Variable phenotypes of r(9) patients could be explained by critical regions and genes of DOCK8, DMRT, SMARCA2, CD274, IL33, PTPRD, CER1, FREM1 for 9p deletions, and the EHMT1 gene for 9q34 deletion syndrome. This interactive registry of r(9) could provide information for cytogenomic diagnosis, genetics counseling and clinical management. K E Y W O R D S clinical and cytogenomic findings, double stand breaks repairing, mechanism of ring chromosome formation, ring chromosome 9, whole genome sequencing 1 | INTRODUCTION Constitutional ring chromosomes which can involve any one of the 22 autosomes and sex chromosomes occur in about 1/50,000 newborns (Kosztolányi, 1987). Ring chromosomes arise typically from the breakage and subsequent fusion of both chromosome arms. Based on the integrity of genetic material, there are two types of ring chromosomes. One type is a complete ring resulting from subtelomeric fusion without any significant loss of genetic material, and the other type of incomplete ring shows distal or interstitial deletions and

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The chromosome 9q subtelomere deletion syndrome

Stewart

Kleefstra²

2007

American J of Med Genetics Pt C

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The chromosome 9q subtelomere deletion syndrome (9qSTDS) is among the first and most common clinically recognizable syndromes to arise from widespread testing by fluorescent in situ hybridization (FISH) of subtelomere deletions. There are about 50 reported cases worldwide. Affected individuals invariably have severe hypotonia with speech and gross motor delay. The facial gestalt is distinct and features absolute or relative micro- or brachycephaly, hypertelorism, synophrys, and/or arched eyebrows, mid-face hypoplasia, a short nose with upturned nares, a protruding tongue with everted lower lip and down-turned corners of the mouth. Approximately half of affected individuals have congenital heart defects (primarily ASD or VSD). A significant minority have epilepsy and/or behavioral and sleep disturbances. A variety of other major and minor eye, ear, genital, and limb anomalies have been reported. Most patients have sub-microscopic deletions of the subtelomere region of chromosome 9q34.3 that range from <400 kb to >3 Mb. The 9qSTDS is caused by haplo-insufficiency of EHMT1, a gene whose protein product (Eu-HMTase1) is a histone H3 Lys 9 (H3-K9) methyltransferase. This was established by identification of three patients with features of the syndrome and either mutations or a balanced translocation in EHMT1. H3-K9 histone methylation is restricted to the euchromatin of mammals and functions to silence individual genes. Deletion size does not correlate with the severity of the 9qSTDS since patients with mutations in EHMT1 are as severely affected as those with submicroscopic deletions. Patients clinically suspected of having the 9qSTDS but with normal subtelomere deletion testing by FISH or MLPA should be considered for detailed 9q MLPA analysis and/or sequencing of EHMT1. EHMT1 is another example in the growing list of genes responsible for brain development that appear to play a role in chromatin remodeling. Published 2007 Wiley-Liss, Inc.

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Ring chromosome 9 [r(9)(p24q34)]: A report of two cases

Cited by 19 publications

References 23 publications

Ring chromosome 9 in a girl with developmental delay and dysmorphic features: Case report and review of the literature

Ring chromosome 9 in a girl with developmental delay and dysmorphic features: Case report and review of the literature

Ring chromosome formation by intra‐strand repairing of subtelomeric double stand breaks and clinico‐cytogenomic correlations for ring chromosome 9

The chromosome 9q subtelomere deletion syndrome

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