Chromosome 16 Abnormalities in Embryos and in Sperm from a Male with a Fragile Site at 16q22.1

Martorell, M R; Martínez-Pasarell, O.; López, Ober Van Gómez; Polo, A.; Sandalinas, M.; Garcia-Guixé, Elena; Bassas, Lluís

doi:10.1159/000357411

Cited by 6 publications

(5 citation statements)

References 17 publications

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“…Fragility at 16q22 has since been implicated in a wide spectrum of neurological disorders (Demirhan et al 2006; Kerbeshian et al 2000) as well as in other conditions such as neutropenia (Glasser et al 2006; Tassano et al 2010) and cleft palate (Bettex et al 1998; Dunner et al 1983; Janiszewska-Olszowska et al 2013; McKenzie et al 2002). A recent study also reported elevated fragile site formation at 16q22.1 in an embryo from a couple who had difficulty achieving pregnancy and in the sperm from the father (Martorell et al 2014). However, cytogenetic breakage and potential disease-associated gene(s) at this locus are yet to be molecularly characterized.…”

Section: 2 Early History Of Chromosome Fragile Site Discoveries Rementioning

confidence: 85%

Fragility Extraordinaire: Unsolved Mysteries of Chromosome Fragile Sites

Feng

Chakraborty

2017

Advances in Experimental Medicine and Biology

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Chromosome fragile sites are a fascinating cytogenetic phenomenon now widely implicated in a slew of human diseases ranging from neurological disorders to cancer. Yet, the paths leading to these revelations were far from direct, and the number of fragile sites that have been molecularly cloned with known disease-associated genes remains modest. Moreover, as more fragile sites were being discovered, research interests in some of the earliest discovered fragile sites ebbed away, leaving a number of unsolved mysteries in chromosome biology. In this review we attempt to recount some of the early discoveries of fragile sites and highlight those phenomena that have eluded intense scrutiny but remain extremely relevant in our understanding of the mechanisms of chromosome fragility. We then survey the literature for disease association for a comprehensive list of fragile sites. We also review recent studies addressing the underlying cause of chromosome fragility while highlighting some ongoing debates. We report an observed enrichment for R-loop forming sequences in fragile site-associated genes than genomic average. Finally, we will leave the reader with some lingering questions to provoke discussion and inspire further scientific inquiries.

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Section: 2 Early History Of Chromosome Fragile Site Discoveries Rementioning

confidence: 85%

Fragility Extraordinaire: Unsolved Mysteries of Chromosome Fragile Sites

Feng

Chakraborty

2017

Advances in Experimental Medicine and Biology

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“…Previous case report and clinical study both indicated that embryos from mosaic fragile carriers have certain ratio of dup or del chromosome which is related with its fragile sites. 21,22 Luo et al studied 12 couples with heterozygous mosaic fragile 16q22 on their chromosomes. These couples underwent preimplantation genetic testing for their embryos.…”

Section: Discussionmentioning

confidence: 99%

Genetic Analysis of a Mosaic Fra(16)(q22)/Del(16)(q22) Karyotype in a Primary Infertile Woman

He,

Wang,

et al. 2024

IJWH

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Fragile sites are specific chromosomal regions showing gaps, poor staining, contractions, or even breaks in the chromosomes. These spontaneous and heritable fragile sites are prone to structural variations which can lead to adverse reproductive outcomes. This paper aims to present a specific case study of a female patient, with a mosaic karyotype involving chromosome 16q22 fragile site which is very rare in clinic and her experience of infertility. Case Presentation: A 37-year-old woman is diagnosed with ten-year primary infertility. She worked in a factory, and she was occasionally exposed to paint. She underwent two cycles of follicular monitoring with intrauterine insemination (IUI) using her husband's sperm six years ago but failed. Most of her prepregnancy tests were normal, except a not smooth right fallopian tube. Her G-band karyotype of peripheral blood lymphocytes was mos 46, XX, del(16)(q22)[40]/46, XX, fra(16)(q22)[29]/46, XX, fra( 16)tr( 16) (q22)[3]/46, XX[28] which inherited from her mother. The SCE assay detected a significantly higher frequency of SCEs in the 16q region of the patient's chromosomes compared to her mother and a healthy control. However, the average SCEs per chromosome were quite close. Moreover, copy number variation (CNV) sequencing showed no deletion nor duplication at 16q22. Conclusion:Infertility cannot be completely attributed to the fragile site on chromosome 16q22. Assisted reproductive technology combined with preimplantation genetic testing may help in achieving a healthy live birth.

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“…Aswini reported a non-consanguineous couple with repeated pregnancy loss who presented with FRA16B expression (Aswini et al, 2012). Recently, Martorell reported a couple with difficulty achieving pregnancy, where the wife was a carrier of t(11;22) (q23;q11.2) and the husband had a high expression of fragile site at 16q22.1 (FRA16B/C) in his peripheral blood lymphocytes (Martorell et al, 2014). The husband's sperm and the embryos both showed chromosome 16 abnormalities, indicating that the fragile site at 16q22.1 might cause chromosomal disorders involving the same breakpoint and non-disjunction during meiosis, thereby leading to pregnancy losses.…”

Section: Discussionmentioning

confidence: 99%

“…Chromosome 16q22.1 contains two fragile sites, FRA16B and FRA16C (Martorell et al, 2014). Previously, these fragile sites were not associated with either clinical problems or phenotypic effects (Schmid et al, 1986).…”

Section: Discussionmentioning

confidence: 99%

De novo c.2455C>T mutation of NPR2 gene in a fetus with shortened long bones and a ventricular septal defect conceived by a mother with a fragile site at 16q22.1 and a father with a rare heterochromatic variant of chromosome 4 from Vietnam

Nguyen

et al. 2021

Molec Gen & Gen Med

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Background A heterozygous natriuretic peptide receptor 2 (NPR2) gene c.2455C>T mutation was identified as a cause of familial idiopathic short stature (ISS). Only two cases with this mutation were reported previously, and the probands with ISS had no organ system defects. Methods Next‐generation sequencing (NGS) was performed on an amniotic fluid DNA sample of a fetus with shortened long bones and a small ventricular septal defect detected by an obstetric ultrasound examination. The pathogenic variant of the fetus was confirmed by Sanger sequencing. Sanger sequencing, G‐banded, and C‐banded karyotyping of the fetus's parents were subsequently performed. Results A de novo NPR2 gene c.2455C>T, p.(Arg819Cys) mutation was identified in the fetus. No microdeletion or microduplication was identified in the fetus by copy number variation sequencing with a maximum resolution of 400 kb. The two previous miscarriages experienced by the fetus's parents were interpreted as a result of chromosomal aberrations, including a maternal fragile site at 16q22.1 and a rare paternal variant involving in a large G‐band‐positive and C‐band‐positive block of paracentric heterochromatin of chromosome 4p. Conclusion This report provides clinical signs of a de novo heterozygous NPR2 gene c.2455C>T mutation in the fetus and shows paternal chromosomal aberrations causing repeated pregnancy loss.

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Chromosome 16 Abnormalities in Embryos and in Sperm from a Male with a Fragile Site at 16q22.1

Cited by 6 publications

References 17 publications

Fragility Extraordinaire: Unsolved Mysteries of Chromosome Fragile Sites

Fragility Extraordinaire: Unsolved Mysteries of Chromosome Fragile Sites

Genetic Analysis of a Mosaic Fra(16)(q22)/Del(16)(q22) Karyotype in a Primary Infertile Woman

De novo c.2455C>T mutation of NPR2 gene in a fetus with shortened long bones and a ventricular septal defect conceived by a mother with a fragile site at 16q22.1 and a father with a rare heterochromatic variant of chromosome 4 from Vietnam

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