A report of three patients with an interstitial deletion of chromosome 15q24. Am J Med Genet A

Department of Pathology & Laboratory Medicine, Drexel University, Filadelfia, Pennsylvania, United States
American Journal of Medical Genetics Part A (Impact Factor: 2.16). 08/2005; 137(1):65-71. DOI: 10.1002/ajmg.a.30836
Source: PubMed


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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    • "Microdeletion of 15q24 was first reported by Cushman et al. in three cases detected by FISH (Cushman et al., 2005). "
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    ABSTRACT: We report a 9-year-old girl with 3 Mb interstitial deletion of chromosome 15q24 identified by oligonucleotide array comparative hybridization. She is of Chinese ancestry and shared some typical features of previously reported 15q24 deletion cases such as mild dysmorphism with developmental and speech delay. She also had mild hearing loss that was reported in one other case. We compared all 19 cases that are identified from array-CGH. The deletion occurred within an 8.3 Mb region from 15q23 to 15q24.3. The minimum overlapping deleted region is less than 0.5 Mb from 72.3 Mb to 72.7 Mb. The functions of the nine annotated genes within the region and how they might contribute to the microdeletion phenotype are discussed.
    Twin Research and Human Genetics 08/2011; 14(4):333-9. DOI:10.1375/twin.14.4.333 · 2.30 Impact Factor
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    • "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 . They concluded that the majority of these cases shared developmental delay , growth deficiency , hypotonia , skeletal abnormalities , urogenital system defects , and similar fa"
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    ABSTRACT: 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.
    Human Genetics 07/2009; 126(4):589-602. DOI:10.1007/s00439-009-0706-x · 4.82 Impact Factor
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    • "Importantly, 60% of persons affected with Kartagener syndrome (immotile cilia syndrome) demonstrate a chromosomal abnormality that localizes to 15q24-25 (Geremek et al, 2006). In addition, a case report describing 2 male children with interstitial deletions of 15q24 describes patients with hypotonia, dysmorphic facial features, and eye abnormalities , as well as genitourinary defects, specifically microphallus and a small scrotal sac in one child and hypospadias in the other (Cushman et al, 2005). Another study localizes the 15q24 microdeletion syndrome to an area that includes the LOXL1 gene and describes 4 human male patients who present with joint laxity/scoliosis, developmental delay, growth retardation and low body weight, characteristic facial anomalies , eye abnormalities, anomalies of the hands and feet, hypospadias (3 of 4), hearing loss (2 of 4), and recurrent chest infections (2 of 4; Sharp et al, 2007). "
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    ABSTRACT: Our objective was to investigate the genitourinary defects and fertility of the male lysyl oxidase-like 1 gene (Loxl1) knockout (Loxl1(-/-)) mouse, with particular attention to fecundity and testicular, epididymal, gubernacular, and penile histopathology, which may lead us to a better understanding of the role of the elastin-homeostasis gene, LOXL1, in male sexual development. Genital morphometric evaluation of 6- to 9-month-old male Loxl1(-/-) mice (n = 26) was compared with C57Bl/6 controls (n = 24). Measurements included: body weight, scrotal development, evidence of feminization (nipples or vaginal pouch), penile malformations, anogenital distance, and absence/presence and size of perineal bulge. Sperm production was estimated using a standardized technique. A breeding program was conducted to determine how much of the infertility observed in Loxl1(-/-) pairs was due to the male factor. Finally, we performed histopathologic comparison of the genitourinary organs of Loxl1(-/-) and control mice. Loxl1(-/-) mice weighed less than their age-matched C57Bl/6 counterparts (P < .001). Size-adjusted perineal bulge was larger (P < .001), and resting location of the gonads was higher intra-abdominally (P = .048) in the Loxl1(-/-) mice. Estimates of daily sperm counts revealed that the Loxl1(-/-) mice had lower sperm production (P = .048). Loxl1(-/-) males bred with control females demonstrated relative fecundity values intermediate between Loxl1(-/-) pairs (lowest fecundity) and control pairs (highest fecundity), suggesting a component of male-factor infertility. No histologic differences were noted using hematoxylin-eosin or specialized elastin staining of the gonads, gubernaculum, and penis. Although further studies are warranted, these findings suggest a subtle and likely multifactorial role of the LOXL1 protein in male sexual development and fertility.
    Journal of Andrology 02/2009; 30(4):452-9. DOI:10.2164/jandrol.108.006122 · 2.47 Impact Factor
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