Authors: M Paglia, M Severino, R Gatto...

Otodental syndrome is a rare autosomal dominant condition characterised by a dental phenotype known as globodontia often associated with high-frequency hearing loss. Globodontia occurs both in the decidous and permanent dentition and affects canine and molar teeth.

Topics: Tooth Abnormalities; Chromosomes, Human, Pair 11; Arthrogryposis; Coloboma; Hearing Loss, Sensorineural; Chromosome Deletion; Chromosome Disorders; Humans

PubMed: 37668456
DOI: 10.23804/ejpd.2023.24.03.03

Authors: Pablo Azurmendi

Topics: Chromosome Deletion; Humans; Williams Syndrome

PubMed: 23335714
DOI: No ID Found

Authors: Amal M Mohamed, Alaa K Kamel, Maha M Eid...

BACKGROUND

This study aimed to delineate the clinical phenotype of patients with 9p deletions, pinpoint the chromosomal breakpoints, and identify the critical region for trigonocephaly, which is a frequent finding in 9p terminal deletion.

METHODS

We investigated a cohort of nine patients with chromosome 9p terminal deletions who all displayed developmental delay, intellectual disability, hypotonia, and dysmorphic features. Of them, eight had trigonocephaly, seven had brain anomalies, seven had autistic manifestations, seven had fair hair, and six had a congenital heart defect (CHD).

RESULTS

Karyotyping revealed 9p terminal deletion in all patients, and patients 8 and 9 had additional duplication of other chromosomal segments. We used six bacterial artificial chromosome (BAC) clones that could identify the breakpoints at 17-20 Mb from the 9p terminus. Array CGH identified the precise extent of the deletion in six patients; the deleted regions ranged from 16 to 18.8 Mb in four patients, patient 8 had an 11.58 Mb deletion and patient 9 had a 2.3 Mb deletion.

CONCLUSION

The gene deletion in the 9p24 region was insufficient to cause ambiguous genitalia because six of the nine patients had normal genitalia. We suggest that the critical region for trigonocephaly lies between 11,575 and 11,587 Mb from the chromosome 9p terminus. To the best of our knowledge, this is the minimal critical region reported for trigonocephaly in 9p deletion syndrome, and it warrants further delineation.

Topics: Chromosome Deletion; Chromosomes; Craniosynostoses; Egypt; Humans; Karyotyping

PubMed: 34609792
DOI: 10.1002/mgg3.1829

Review

Authors: Hui-Hui Xu, Yang Zhang, Zhe-Hang He...

BACKGROUND

Xq22.1-q22.3 deletion is a rare chromosome aberration. The purpose of this study was to identify the correlation between the phenotype and genotype of chromosome Xq22.1-q22.3 deletions.

METHODS

Chromosome aberrations were identified by copy number variation sequencing (CNV-seq) technology and karyotype analysis. Furthermore, we reviewed patients with Xq22.1-q22.3 deletions or a deletion partially overlapping this region to highlight the rare condition and analyse the genotype-phenotype correlations.

RESULTS

We described a female foetus who is the "proband" of a Chinese pedigree and carries a heterozygous 5.29 Mb deletion (GRCh37: chrX: 100,460,000-105,740,000) in chromosome Xq22.1-q22.3, which may affect 98 genes from DRP2 to NAP1L4P2. This deletion encompasses 7 known morbid genes: TIMM8A, BTK, GLA, HNRNPH2, GPRASP2, PLP1, and SERPINA7. In addition, the parents have a normal phenotype and are of normal intelligence. The paternal genotype is normal. The mother carries the same deletion in the X chromosome. These results indicate that the foetus inherited this CNV from her mother. Moreover, two more healthy female family members were identified to carry the same CNV deletion through pedigree analysis according to the next-generation sequencing (NGS) results. To our knowledge, this family is the first pedigree to have the largest reported deletion of Xq22.1-q22.3 but to have a normal phenotype with normal intelligence.

CONCLUSIONS

Our findings further improve the understanding of the genotype-phenotype correlations of chromosome Xq22.1-q22.3 deletions.This report may provide novel information for prenatal diagnosis and genetic counselling for patients who carry similar chromosome abnormalities.

Topics: Pregnancy; Female; Humans; Pedigree; DNA Copy Number Variations; Phenotype; Chromosome Aberrations; Chromosome Deletion; Chromosomes; Mitochondrial Precursor Protein Import Complex Proteins

PubMed: 37217926
DOI: 10.1186/s12920-023-01547-2

Authors: Francisco M Barriga, Kaloyan M Tsanov, Yu-Jui Ho...

The most prominent homozygous deletions in cancer affect chromosome 9p21.3 and eliminate CDKN2A/B tumor suppressors, disabling a cell-intrinsic barrier to tumorigenesis. Half of 9p21.3 deletions, however, also encompass a type I interferon (IFN) gene cluster; the consequences of this co-deletion remain unexplored. To functionally dissect 9p21.3 and other large genomic deletions, we developed a flexible deletion engineering strategy, MACHETE (molecular alteration of chromosomes with engineered tandem elements). Applying MACHETE to a syngeneic mouse model of pancreatic cancer, we found that co-deletion of the IFN cluster promoted immune evasion, metastasis and immunotherapy resistance. Mechanistically, IFN co-deletion disrupted type I IFN signaling in the tumor microenvironment, leading to marked changes in infiltrating immune cells and escape from CD8 T-cell surveillance, effects largely driven by the poorly understood interferon epsilon. These results reveal a chromosomal deletion that disables both cell-intrinsic and cell-extrinsic tumor suppression and provide a framework for interrogating large deletions in cancer and beyond.

Topics: Animals; Mice; Chromosome Deletion; Chromosomes; Immune Evasion; Interferons; Neoplasms; Tumor Microenvironment; Tandem Repeat Sequences

PubMed: 36344707
DOI: 10.1038/s43018-022-00443-5

Review

Authors: C Dowman, D Lockwood, J Allanson...

We report a female with a deletion of 9p and concomitant duplication of 16q [46,XX,-9,+der(9),t(9;16)(p24;q13)]. Parental chromosome analysis showed a balanced maternal translocation [46,XX,t(9;16)(p24;q13)]. Three other cases of translocations involving chromosomes 9 and 16 have been reported, one of them with identical breakpoints. A review of published reports of deletion 9p and duplication 16q is presented, and a comparison is made with previously described cases.

Topics: Abnormalities, Multiple; Chromosome Banding; Chromosome Deletion; Chromosomes, Human, Pair 16; Chromosomes, Human, Pair 9; Female; Humans; Infant, Newborn; Karyotyping; Multigene Family; Translocation, Genetic

PubMed: 2671373
DOI: 10.1136/jmg.26.8.525

Authors: Amit Khot

Topics: Humans; Multiple Myeloma; Prognosis; Chromosome Deletion; In Situ Hybridization, Fluorescence

PubMed: 36929439
DOI: 10.1182/blood.2022018967

Review

Authors: Massimo Pisano, Giuseppe Sangiovanni, Francesco D'Ambrosio...

BACKGROUND Long arm (q) deletion syndrome of chromosome 18 is a congenital chromosomal disorder. The specialist dental management of patients with 18q deletion is a challenge, as these individuals fall into the category of patients with special needs. The aim of this work was to describe the surgical and dental management in hospital of a patient with long arm deletion syndrome of chromosome 18 (18q). CASE REPORT An 8-year-old patient with deletion syndrome of chromosome 18 (18q) was referred to the Department of Dentistry and Oral Surgery. The patient presented dental pain and difficult feeding. The examination of the oral cavity revealed a destructive carious lesion of the lower right second deciduous molar and the need to perform a frenectomy due to the short lingual frenulum, which limited the movements of the tongue. Given the complex management of the patient, it was necessary to carry out surgical procedures in the operating room. Frenectomies of the lower labial and lingual frenulum were carried out with the aid of an electric scalpel with an ultra-sharp microdissection needle. At 2-month follow-up, the patient presented with good extraction site healing and satisfactory lingual mobility, along with improvements of speech and feeding. CONCLUSIONS Dental involvement in patients with deletion syndrome of the long arm of chromosome 18 is poorly documented in the literature. The hospital regimen appears to be the criterion standard for the management of the patient with long arm deletion syndrome of chromosome 18.

Topics: Child; Chromosome Deletion; Chromosome Disorders; Chromosomes, Human, Pair 18; Humans; Syndrome; Tongue Diseases

PubMed: 35746851
DOI: 10.12659/AJCR.936142

Review

Authors: Marian Grade, Michael J Difilippantonio, Jordi Camps...

Chromosomal abnormalities are a defining feature of solid tumors. Such cytogenetic alterations are mainly classified into structural chromosomal aberrations and copy number alterations, giving rise to aneuploid karyotypes. The increasing detection of these genetic changes allowed the description of specific tumor entities and the associated patterns of gene expression. In fact, tumor-specific landscapes of gross genomic copy number changes, including aneuploidies of entire chromosome arms and chromosomes result in a global deregulation of the transcriptome of cancer cells. Furthermore, the molecular characterization of cytogenetic abnormalities has provided insights into the mechanisms of tumorigenesis and has, in a few instances, led to the clinical implementation of effective diagnostic and prognostic tools, as well as treatment strategies that target a specific genetic abnormality.

Topics: Animals; Chromosome Aberrations; Chromosome Deletion; Gene Amplification; Gene Dosage; Humans; Neoplasms; Translocation, Genetic

PubMed: 26376875
DOI: 10.1007/978-3-319-20291-4_6

Authors: Shumin Chen, Feihong Ren, Lei Zhang...

The types of mutations and their corresponding frequencies are difficult to measure in complex genomes. In this study, a high-throughput method was developed to identify spontaneous loss-of-function alleles for the resistance gene N and the transgenic avirulence gene P50 in allotetraploid tobacco. A total of 2134 loss-of-function alleles of the N gene were identified after screening 14 million F hybrids. Analysis of these mutants revealed striking evolutionary patterns for genes in polyploids. Only 14 of the loss-of-function mutations were caused by spontaneous point mutations or indels, while the others were caused by homeologous recombination (with a frequency of ∼1/12 000) or chromosome loss (∼1/15 000). Loss of the chromosome with the P50 insertion occurred at a similar frequency (∼1/13 000), and the frequency of spontaneous segmental deletion in this chromosome was ∼1/16 000. Both homeologous recombination and chromosome loss considerably decreased the viability of the mutants. Our data suggest that the high mutation rate in polyploids is probably due to the occurrence of homeologous recombination and the tolerance of large mutations such as chromosome loss in polyploid genomes. Frequent mutations tend to drive polyploids to extinction unless a novel mutation helps the polyploid to effectively compete with diploids or find a new ecological niche.

Topics: Chromosome Deletion; Genome, Plant; INDEL Mutation; Models, Genetic; Polyploidy; Recombination, Genetic; Tobacco Products

PubMed: 29734001
DOI: 10.1016/j.molp.2018.04.009