A Marfan syndrome‐like phenotype caused by a neocentromeric supernumerary ring chromosome 15

Quinonez, Shane C.; Gelehrter, Thomas D.; Uhlmann, Wendy R.

doi:10.1002/ajmg.a.38000

Cited by 3 publications

(1 citation statement)

References 31 publications

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“…sSMCs may present as various forms, including inverted duplicated (inv dup), complex rearranged, minute, ring or neocentric chromosomes (6). Most sSMCs result from short arms and pericentric regions of acrocentric chromosomes, among which sSMC on chromosome 15 [sSMC (15)] is the most common (7)(8)(9). To date, the genotype-phenotype association between sSMCs and male infertility has remained elusive.…”

Section: Introductionmentioning

confidence: 99%

Molecular cytogenetic characterization of small supernumerary marker 15 in infertile male: A case report

et al. 2020

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Small supernumerary marker chromosomes (sSMCs) are defined as structurally abnormal chromosomes that may be detected pre-or postnataly in patients with developmental and/or mental retardation or infertility. sSMC on chromosome 15 accounts for the highest proportion of all sSMCs and may be detected in subfertile individuals. The present study reports the case of a male patient with oligoasthenoteratozoospermia and an sSMC. The sSMC was identified and characterized according to G-banding analysis, chromosomal microarray analysis (CMA) and fluorescence in situ hybridization (FISH) analysis. Chromosomal karyotype analysis suggested that the patient presented with 47,XY,+mar. CMA was used to characterize the sSMC, which revealed a 0.44-Mb microduplication in 6q25.3q26. Subsequently, FISH using centromere-specific probes for chromosomes 13/21, 14/22 and 15 was applied to identify the origin of the sSMC, which was finally determined to be inverted duplicated(15) (q11.2). It was hypothesized that heterochromatin in the sSMC is responsible for the patient's fertility problem. The presence of heterochromatin may disrupt regular meiosis, thereby affecting normal spermatogenesis. Impaired spermatogenesis in infertile males with an sSMC derived from chromosome 15 was also reviewed by searching published literature and the sSMC database (http://ssmc-tl.com/sSMC.html). For patients with low sperm parameters and complete absence of spermatozoa in the ejaculate, including infertile males with an sSMC with spermatozoa, intracytoplasmic sperm injection is considered as an effective assisted reproductive technique. It may be concluded that molecular cytogenetic techniques are critical tools for delineating sSMCs in infertile males and may be beneficial in identifying sSMC carriers to ensure they receive clinical genetic counseling.

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Section: Introductionmentioning

confidence: 99%

Molecular cytogenetic characterization of small supernumerary marker 15 in infertile male: A case report

et al. 2020

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Intragenic multi-exon deletion in the FBN1 gene in a child with mildly dilated aortic sinus: a retrotransposal event

et al. 2017

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Marfan syndrome is an autosomal dominant disorder affecting mainly the skeletal, ocular and cardiovascular systems. Most cases are caused by mutations in the fibrillin-1 gene (FBN1), although there are some reports on deletions involving FBN1 and other additional genes. We report a male patient who was first evaluated at 4 years of age. Echocardiogram showed a mildly dilated aortic sinus. He also had a history of muscular ventral septal defect which was closed spontaneously and trivial mitral regurgitation. Other phenotypic features include frontal bossing, anteverted ears, joint hyperlaxity, learning disability, skin striae, and height and weight in the >97th centile but no other diagnostic findings of MFS and does not fulfill the revised Ghent criteria. Chromosomal microarray analysis showed a deletion of approximately 36.8 kb at 15q21.1, which starts in intron 6 and ends in intron 9 and includes three FBN1 exons. Sequence analysis of the breakpoint region confirmed the deletion and revealed a concomitant insertion of a retrotransposon within the intron 6/intron 9 region. The intragenic deletion of exons 7-9 was likely the result of a retrotransposition event by a MAST2-SVA element mediated by repetitive sequences.

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Ring chromosome 15 – cytogenetics and mapping arrays: a case report and review of the literature

et al. 2018

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BackgroundRing chromosome 15 has been associated in previous studies with different clinical characteristic such as cardiac problems, digit and musculoskeletal abnormalities, and mental and motor problems among others. Only 97 clinical cases of ring chromosome 15 syndrome have been reported since 1966 and a common phenotype for these patients has not been established.Case presentationThe present case report describes a 15-month-old girl from the Amazon region of Ecuador, of Mestizo ancestry, who after cytogenetic tests showed a 46,XX,r(15) karyotype in more than 70% of metaphases observed. Her parents were healthy and non-related. The pregnancy was complicated and was positive for intrauterine growth retardation. Her birth weight was 1950 g, her length was 43.5 cm, and she had a head circumference of 29.3. In addition to postnatal growth delay, she had scant frontal hair, small eyes, hypertelorism, low-set of ears, flattened nasal bridge, anteverted nostrils, down-turned mouth, three café au lait spots, and delayed dentition.ConclusionsDespite the frequency of some phenotypes expressed in the different clinical cases reviewed and the present case, a common phenotype for patients with ring 15 could not be determined and it is restricted to the region of the chromosome lost during the ring formation.

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A Marfan syndrome‐like phenotype caused by a neocentromeric supernumerary ring chromosome 15

Cited by 3 publications

References 31 publications

Molecular cytogenetic characterization of small supernumerary marker 15 in infertile male: A case report

Molecular cytogenetic characterization of small supernumerary marker 15 in infertile male: A case report

Intragenic multi-exon deletion in the FBN1 gene in a child with mildly dilated aortic sinus: a retrotransposal event

Ring chromosome 15 – cytogenetics and mapping arrays: a case report and review of the literature

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