Molecular characterization of a patient with an interstitial 1q deletion [del(1)(q24.1q25.3)] and distinctive skeletal abnormalities

Descartes, Maria; Hain, Julie Zenger; Conklin, Michael; Franklin, Judith; Mikhail, Fady M.; Lachman, Ralph S.; Nolet, Serge; Messiaen, Ludwine

doi:10.1002/ajmg.a.32550

Cited by 18 publications

(30 citation statements)

References 34 publications

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“…In contrast to the literature, only 2% of all were deletions in our study. Interstitial deletions in chromosomes 1 and 5 are rarely reported (23,24). To our knowledge, interstitial deletions of 5q13-q22 and 1q22-q25 chromosome regions in prenatal diagnosis were observed for first time in our study.…”

Section: Resultssupporting

confidence: 48%

Rare structural chromosomal abnormalities in prenatal diagnosis; clinical and cytogenetic findings on 10125 prenatal cases

Yakut¹,

Çetin²,

Şi̇mşek³

et al. 2014

TJPATH

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Objective: The aim of this study was presentation of the ultrasonographic findings and perinatal autopsy of cases with rare chromosomal abnormalities. Material and Method:A total of 10125 prenatal cases over 17 years including 8731 amniocentesis, 973 chorionic villus sampling, and 421 fetal blood sampling cases were evaluated for prenatal cytogenetic diagnosis. Conventional cytogenetic studies, fluorescence in situ hybridization studies, and Array-CGH analysis techniques were used for genetic analysis.Results: A structural chromosomal abnormality was observed in 95 cases. The most frequently observed structural abnormalities were balanced translocations with a frequency of 53.7% (51 cases) followed by unbalanced translocations (16.8%), inversions (11.6%), supernumerary marker chromosomes (8.4%), duplications (4.2%), deletions and ring chromosomes (2.1%) and complex translocation (1.1%). rare structural chromosomal abnormalities including de novo balanced translocations, unbalanced translocations, inversions, duplications, deletions, ring chromosomes, and supernumerary marker chromosomes were detected in 24 cases. Conclusion:The rate of rare chromosomal abnormalities varies from 2.4% (South east Ireland) to 12.9% (northern england) in europe with a total rate of 7.4/10 000 births. In our study, the overall rate of chromosomal abnormality in prenatal cytogenetic diagnosis was 3.7%, similar to South east Ireland. ultrasonographic and perinatal autopsy findings of the cases with rare structural chromosomal abnormalities are important for proper genetic counseling for further similar cases.

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Section: Resultssupporting

confidence: 48%

Rare structural chromosomal abnormalities in prenatal diagnosis; clinical and cytogenetic findings on 10125 prenatal cases

Yakut¹,

Çetin²,

Şi̇mşek³

et al. 2014

TJPATH

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“…57 However, the mechanism by which the miR-17 $ 92 cluster regulates skeletal development has not yet been fully elucidated Further associations between miRNAs and human skeletal development have been suggested from reports on patients with deletions or a translocation within chromosome 1q24 resulting in various skeletal abnormalities. [59][60][61][62][63][64] Recently, Ashraf et al reported two additional patients with microdeletions in 1q24q25 that display similar skeletal abnormalities as reported previously (i.e., short stature, brachydactyly, and facial dysmorphism). 65 The deletion mutation in one of these patients narrowed down the critical region causing these skeletal defects to that encoding dynamin-3 (DNM3) and two miRNAs located within intron 14 of this gene (miR-199a and miR-214).…”

Section: Mirnas Regulating Skeletal Development and Homeostasis-evidesupporting

confidence: 53%

MicroRNAs in orthopaedic research: Disease associations, potential therapeutic applications, and perspectives

McAlinden

2017

Journal Orthopaedic Research

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MicroRNAs (miRNAs) are small non-coding RNAs that function to control many cellular processes by their ability to suppress expression of specific target genes. Tens to hundreds of target genes may be affected by one miRNA, thereby resulting in modulation of multiple pathways in any given cell type. Therefore, altered expression of miRNAs (i.e., during tissue development or in scenarios of disease or cellular stress) can have a profound impact on processes regulating cell differentiation, metabolism, proliferation, or apoptosis, for example. Over the past 5-10 years, thousands of reports have been published on miRNAs in cartilage and bone biology or disease, thus highlighting the significance of these non-coding RNAs in regulating skeletal development and homeostasis. For the purpose of this review, we will focus on miRNAs or miRNA families that have demonstrated function in vivo within the context of cartilage, bone or other orthopaedicrelated tissues (excluding muscle). Specifically, we will discuss studies that have utilized miRNA transgenic mouse models or in vivo approaches to target a miRNA with the aim of altering conditions such as osteoarthritis, osteoporosis and bone fractures in rodents. We will not discuss miRNAs in the context skeletal cancers since this topic is worthy of a review of its own. Overall, we aim to provide a comprehensive description of where the field currently stands with respect to the therapeutic potential of specific miRNAs to treat orthopaedic conditions and current technologies to target and modify miRNA function in vivo. KeywordsMicroRNAs (miRNAs); cartilage; bone; skeletal development; osteoarthritis MicroRNA (miRNAs) are small non-coding RNA molecules (typically 19-24 nucleotides in length) that function in RNA silencing and post-transcriptional regulation (suppression) of gene expression. 1 While the majority of miRNAs are located within the cell, some miRNAs, commonly known as circulating miRNA or extracellular miRNA, have also been detected outside the cell in the extracellular matrix, in various biological fluids, or in cell culture. HHS Public Access Author Manuscript Author ManuscriptAuthor ManuscriptAuthor Manuscript miRNAs were first discovered over 20 years ago in the nematode Caenorhabditis elegans with the identification of the developmental regulator lin-4. 3 Since then, thousands of miRNAs have been identified and investigated, with a wide distribution in animals, plants, and viruses. 4 MicroRNAs are ubiquitously expressed in different organisms, and many of them are phylogenetically conserved. 5 To date, over 28,000 miR-NAs from various species are listed in the miRBase website (http://www.mirbase.org). Specifically, 2,588 mature miRNAs have been identified in humans and 1,915 mature miRNAs have been reported in mice.With respect to miRNA biosynthesis, transcription of miRNA genes that are located either intergenically or intragenically is mediated primarily by RNA polymerase II in eukaryotes, although RNA polymerase III has also been shown to transcrib...

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“…LHX4 (LIM homeobox gene 4) and CENPL (centromeric protein L) were suggested to be the primary candidate genes for growth retardation in the 1q25-q32 region. Initially, several studies indicated that growth retardation was likely attributed to the low serum GH levels resulting from heterozygous deletion of LHX4 in patients [6-8]. Heterozygous mutations of LHX4 can lead to abnormalities of pituitary and cerebellum, the deficiency of growth hormone, and then growth retardation [13].…”

Section: Discussionmentioning

confidence: 99%

“…Mice with null ASTN1 showed smaller sizes of cerebella, poorer balance and coordination, reduction in migration rates [17]. Of the eleven postnatal deletion cases harboring ASTN1 [2,3,6-8,10], six displayed brain structure malformations [2,3,7,10], four were normal by MRI analysis [8,10], and the remaining one is unknown. We concluded that heterozygous ASTN1 deletion could be an important cause of the mental retardation in 1q25-32 deletion patients.…”

Section: Discussionmentioning

confidence: 99%

“…As far as we know, 7 intermediate 1q deletions (including ours) were tested by microsatellite analysis to investigate the origin of the genomic deletion. Only one deletion [3] was derived from mother, the remaining six [4-6,8,12] were all of paternal origins. However, distinctive features between the 1q25-32 deletion patients who have different parental origin were not observed.…”

Section: Discussionmentioning

confidence: 99%

See 1 more Smart Citation

1q25.2-q31.3 Deletion in a female with mental retardation, clinodactyly, minor facial anomalies but no growth retardation

Wang

Meng

et al. 2013

Mol Cytogenet

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The reports of 1q25-32 deletion cases are rare. We reported here an 11-year-old Chinese Han female with an interstitial 1q25 deletion displaying mental retardation, clinodactyly of the 5th finger and minor facial anomalies. Notably, the patient did not present growth retardation which is quite common in patients with 1q25-32 deletion encompassing LHX4. The heterozygous deletion in this patient was characterized as 46,XX,del(1)(q25.2-q31.3) with a length of 20.5 Mb according to SNP-array test results. STRP (Short Tandem Repeat Polymorphism) analysis of the family trio indicated the genomic abnormality was de novo with paternal origin. After a genotype-phenotype analysis, we proposed here the loss of a 3.1 Mb critical region including 24 genes within 1q25.2 (chr1:174.5-177.6 Mb, build 36) may account for the mental retardation in patients with 1q25-32 deletion.

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Molecular characterization of a patient with an interstitial 1q deletion [del(1)(q24.1q25.3)] and distinctive skeletal abnormalities

Cited by 18 publications

References 34 publications

Rare structural chromosomal abnormalities in prenatal diagnosis; clinical and cytogenetic findings on 10125 prenatal cases

Rare structural chromosomal abnormalities in prenatal diagnosis; clinical and cytogenetic findings on 10125 prenatal cases

MicroRNAs in orthopaedic research: Disease associations, potential therapeutic applications, and perspectives

1q25.2-q31.3 Deletion in a female with mental retardation, clinodactyly, minor facial anomalies but no growth retardation

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