A patient with a de novo 15q24q26.1 interstitial deletion, developmental delay, mild dysmorphism, and very blue irises

Spruijt, Liesbeth; Engelen, J. J. M.; Bruinen-Smeijsters, I.P.; Albrechts, J. C. M.; Schrander, J. J. P.; Schrander‐Stumpel, Connie

doi:10.1002/ajmg.a.30185

Cited by 7 publications

(8 citation statements)

References 10 publications

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“…Nine cases with deletions involving chromosome 15q22‐q24 (Fig. 4 and Table I) have been reported in the literature [Clark, 1984; Yip et al, 1986; Formiga et al, 1988; Martin et al, 1990; Bettelheim et al, 1998; Smith et al, 2000, Spruit et al, 2004]. However, only one of these patients has a cryptic deletion, similar to Patients 1 and 2 in the present report.…”

Section: Discussionsupporting

confidence: 86%

“…g : del(15)(q21q24) [Formiga et al, 1988]. h : del(15)(q24q26.1) [Spruit et al, 2004]. i : del(15)(q24 → qter) [Bettelheim et al, 1998].…”

Section: Discussionunclassified

“…With the exception of deletions at 15q11‐q13, which results in either Prader–Willi syndrome or Angelman syndrome, constitutional deletions of chromosome 15 are relatively rare. Fewer than 30 patients with deletions in the q2 region of chromosome 15 have been reported to date [Clark, 1984; Yip et al, 1986; Formiga et al, 1988; Martin et al, 1990; Siebler et al, 1995; Bettelheim et al, 1998; Smith et al, 2000; Schinzel, 2001; Schlembach et al, 2001; Tonnies et al, 2001; Nagai et al, 2002; Liehr et al, 2003; Okubo et al, 2003; Biggio et al, 2004; Spruit et al, 2004], with only nine of these patients having interstitial deletions involving 15q22‐q24. Although the phenotype of the nine cases is variable and depends on the extent of the deletion, all affected patients are reported to have significant developmental delays and most have altered muscle tone (typically hypotonia).…”

Section: Introductionmentioning

confidence: 99%

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A report of three patients with an interstitial deletion of chromosome 15q24

Cushman

Torres-Martinez

Cherry

et al. 2005

American J of Med Genetics Pt A

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Partial monosomy of the q2 region of chromosome 15 has been infrequently reported. Moreover, interstitial deletions involving 15q22-q24 have been described in only nine patients to date. The phenotype of these reported individuals is subject to the extent of the deletion but typically includes altered muscle tone and significant developmental delays. In addition, eye abnormalities, such as strabismus, microphthalmia, or colobomas, ear abnormalities including cleft earlobe and preauricular tags, and urogenital defects are common features. Congenital heart defects, diaphragmatic hernia, abnormalities of the central nervous system, and skeletal anomalies have been reported but appear to be less frequent clinical manifestations. In this report, we describe three new patients with interstitial deletions involving 15q24, two with cryptic deletions identified by fluorescence in situ hybridization (FISH) with a probe for the PML gene and one with a cytogenetically visible deletion of 15q22.3-q24. The clinical presentation of these individuals is similar to those previously described and includes global developmental delays, hypotonia, and genital abnormalities in the males. The identification of these three cases demonstrates that the above clinical features are associated with a new cytogenetic deletion syndrome. Furthermore, we suggest that FISH analysis with a probe for the PML gene be performed in patients with these physical findings.

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Section: Discussionsupporting

confidence: 86%

“…g : del(15)(q21q24) [Formiga et al, 1988]. h : del(15)(q24q26.1) [Spruit et al, 2004]. i : del(15)(q24 → qter) [Bettelheim et al, 1998].…”

Section: Discussionunclassified

Section: Introductionmentioning

confidence: 99%

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A report of three patients with an interstitial deletion of chromosome 15q24

Cushman

Torres-Martinez

Cherry

et al. 2005

American J of Med Genetics Pt A

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“…With the exception of the common recurrent 15q11.2q12 deletions which, depending on parental origin, result in either Prader–Willi syndrome or Angelman syndrome, and deletions and duplications in 15q13.3 (Sharp et al 2008; Ben-Shachar et al 2009), rearrangements of chromosome 15q are relatively rare (Cushman et al 2005); those involving the 15q24 region were described in patients with growth deficiency, psychomotor retardation, and birth defects (Bettelheim et al 1998; Clark 1984; Formiga et al 1988; Spruijt et al 2004). Cushman et al (2005) reported three patients with a 15q24 deletion and reviewed the previously reported cases with cytogenetically visible deletions involving the 15q22q24 region.…”

Section: Introductionmentioning

confidence: 99%

Redefined genomic architecture in 15q24 directed by patient deletion/duplication breakpoint mapping

et al. 2009

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We report four new patients with a submicroscopic deletion in 15q24 manifesting developmental delay, short stature, hypotonia, digital abnormalities, joint laxity, genital abnormalities, and characteristic facial features. These clinical features are shared with six recently reported patients with a 15q24 microdeletion, supporting the notion that this is a recognizable syndrome. We describe a case of an ~2.6 Mb microduplication involving a portion of the minimal deletion critical region in a 15-year-old male with short stature, mild mental retardation, attention deficit hyperactivity disorder, Asperger syndrome, decreased joint mobility, digital abnormalities, and characteristic facial features. Some of these features are shared with a recently reported case with a 15q24 microduplication involving the minimal deletion critical region. We also report two siblings and their mother with duplication adjacent and distal to this region exhibiting mild developmental delay, hypotonia, tapering fingers, characteristic facial features, and prominent ears. The deletion and duplication breakpoints were mapped by array comparative genomic hybridization and the genomic structure in 15q24 was analyzed further. Surprisingly, in addition to the previously recognized three low-copy repeat clusters (BP1, BP2, and BP3), we identified two other paralogous low-copy repeat clusters that likely mediated the formation of alternative sized 15q24 genomic rearrangements via non-allelic homologous recombination.

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“…In contrast, interstitial deletion of 15q26 appears to be rare. There have been a few 15q interstitial deletion cases reported, and the majority of them are cytogenetically visible deletions of various sizes in the 15q21.1-26.1 region [Martin et al, 1990;Spruijt et al, 2004]. We present a child with developmental delay, mild dysmorphic features and an apparently balanced translocation t(15;22)(q26.1;q11.2).…”

Section: Introductionmentioning

confidence: 91%

Characterization of a cryptic 3.3 Mb deletion in a patient with a “balanced t(15;22) translocation” using high density oligo array CGH and gene expression arrays

Li¹,

Nimmakayalu²,

Mercer³

et al. 2008

American J of Med Genetics Pt A

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Patients with an apparently balanced translocation and an abnormal phenotype may carry a cryptic deletion/duplication at their translocation breakpoints that may explain their abnormalities. Using microarray CGH (aCGH) and gene expression arrays we studied a child with t(15;22)(q26.1;q11.2), developmental delay and mild dysmorphic features. A high density aCGH study with 244,000 oligo probes demonstrated a 3.3 Mb deletion immediately adjacent to the 15q breakpoint. Gene expression studies with 44,000 oligos displayed an approximately 50% reduction of the expression of IGF1R gene that was translocated to the der(22). There are 18 known or hypothetical protein coding genes within the deleted region according to UniProt, RefSeq, and GenBank mRNA (UCSC HG17, May 2004). Although two of these genes, RGMA and ST8SIA2, play an important role in neural development, the mild phenotype of our patient indicates that loss of one copy of these genes may not be critical developmentally. The 50% reduction of IGF1R expression could be responsible for the growth deficiency in the patient. Reviewing the few 15q26 microdeletion cases that have been characterized by aCGH, we discovered that deletion of the segment including distal 15q26.2 to the proximal part of 15q26.3 is associated with severe phenotypes. Our experience demonstrates that high-density oligonucleotide-based aCGH is a quick and precise way to identify cryptic copy number changes in "balanced translocations." Expression studies can also add valuable information regarding gene expression changes due to a chromosomal rearrangement. Both approaches can assist in the elucidation of the etiology of unexplained phenotypic differences in cases such as this one.

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A patient with a de novo 15q24q26.1 interstitial deletion, developmental delay, mild dysmorphism, and very blue irises

Cited by 7 publications

References 10 publications

A report of three patients with an interstitial deletion of chromosome 15q24

A report of three patients with an interstitial deletion of chromosome 15q24

Redefined genomic architecture in 15q24 directed by patient deletion/duplication breakpoint mapping

Characterization of a cryptic 3.3 Mb deletion in a patient with a “balanced t(15;22) translocation” using high density oligo array CGH and gene expression arrays

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