Clinical and genomic profiling of a patient with a de novo ring chromosome 18: a case report highlighting autoimmune and neurological implications.

Ring chromosome 18 (r(18)) is a rare chromosomal abnormality characterized by the circular rearrangement of chromosome 18, which presents significant challenges in genotype-phenotype correlations due to variability in deletions across the 18p and 18q arms. We report the case of a pediatric patient with a de novo ring chromosome 18, diagnosed by karyotype analysis and confirmed by high-resolution SNP arrays. The patient exhibited pathogenic copy number variants (CNVs) in the 18p11.

Positive predictive values and outcomes for uninformative cell-free DNA tests: An Italian multicentric Cytogenetic and cytogenomic Audit of diagnOstic testing (ICARO study).

Objectives: To establish the positive predictive values (PPV) of cfDNA testing based on data from a nationwide survey of independent clinical cytogenetics laboratories.

Methods: Prenatal diagnostic test results obtained by Italian laboratories between 2013 and March 2020 were compiled for women with positive non-invasive prenatal tests (NIPT), without an NIPT result, and cases where there was sex discordancy between the NIPT and ultrasound. PPV and other summary data were reviewed.

Cytogenetic and Array-CGH Characterization of a Simple Case of Reciprocal t(3;10) Translocation Reveals a Hidden Deletion at 5q12.

Chromosome deletions, including band 5q12, have rarely been reported and have been associated with a wide range of clinical manifestations, such as postnatal growth retardation, intellectual disability, hyperactivity, nonspecific ocular defects, facial dysmorphism, and epilepsy. In this study, we describe for the first time a child with growth retardation in which we identified a balanced t(3;10) translocation by conventional cytogenetic analysis in addition to an 8.6 Mb 5q12 deletion through array-CGH.

gene overexpression in primary plasma cell leukemia with t(11;14)(q13;q32).

Primary plasma cell leukemia (pPCL) is an uncommon form of plasma cell dyscrasia, and the most aggressive of the human monoclonal gammopathies. The t(11;14)(q13;q32) rearrangement is the most common alteration in pPCL, promoting () gene overexpression caused by its juxtaposition with the chromosome region. The () gene maps very close to the gene on chromosome 11, but its overexpression is rarely observed in multiple myeloma.

Overexpression of the LSAMP and TUSC7 genes in acute myeloid leukemia following microdeletion/duplication of chromosome 3.

The 3q13.31 microdeletion syndrome is characterized by developmental delay, postnatal growth above the mean, characteristic facial features, and abnormal male genitalia. Moreover, a frequent deletion in the 3q13.

BCR-ABL1 e6a2 transcript in chronic myeloid leukemia: biological features and molecular monitoring by droplet digital PCR.

The BCR-ABL1 fusion on the Philadelphia (Ph) chromosome is a hallmark of chronic myeloid leukemia (CML). More than 95 % of BCR-ABL1 transcripts in CML are either e13a2 or e14a2 (major breakpoint cluster region or M-bcr), whereas rare BCR-ABL1 transcripts are occasionally observed, accounting for less than 1 % of CML cases. Among these, a very rare fusion transcript joining the first 6 exons of BCR to exon 2 of ABL1 (e6a2) has been reported in various hematological malignancies characterized by an aggressive clinical course.

Absolute quantification of the pretreatment PML-RARA transcript defines the relapse risk in acute promyelocytic leukemia.

In this study we performed absolute quantification of the PML-RARA transcript by droplet digital polymerase chain reaction (ddPCR) in 76 newly diagnosed acute promyelocytic leukemia (APL) cases to verify the prognostic impact of the PML-RARA initial molecular burden. ddPCR analysis revealed that the amount of PML-RARA transcript at diagnosis in the group of patients who relapsed was higher than in that with continuous complete remission (CCR) (272 vs 89.2 PML-RARA copies/ng, p = 0.

ADAMTS2 gene dysregulation in T/myeloid mixed phenotype acute leukemia.

Background: Mixed phenotype acute leukemias (MPAL) include acute leukemias with blasts that express antigens of more than one lineage, with no clear evidence of myeloid or lymphoid lineage differentiation. T/myeloid (T/My) MPAL not otherwise specified (NOS) is a rare leukemia that expresses both T and myeloid antigens, accounting for less than 1% of all leukemias but 89% of T/My MPAL. From a molecular point of view, very limited data are available on T/My MPAL NOS.

5'RUNX1-3'USP42 chimeric gene in acute myeloid leukemia can occur through an insertion mechanism rather than translocation and may be mediated by genomic segmental duplications.

Background: The runt-related transcription factor 1 (RUNX1) gene is a transcription factor that acts as a master regulator of hematopoiesis and represents one of the most frequent targets of chromosomal rearrangements in human leukemias. The t(7;21)(p22;q22) rearrangement generating a 5'RUNX1-3'USP42 fusion transcript has been reported in two cases of pediatric acute myeloid leukemia (AML) and further in eight adult cases of myeloid neoplasms. We describe the first case of adult AML with a 5'RUNX1-3'USP42 fusion gene generated by an insertion event instead of chromosomal translocation.

Myelodysplastic syndrome with 5q deletion following IgM monoclonal gammopathy, showing gene mutation MYD88 L265P.

Patients affected by monoclonal gammopathy of undetermined significance (MGUS) very rarely develop a myelodysplastic syndrome (MDS). However, it was also demonstrated that MGUS patients had a significantly increased risk of developing MDS compared to the general population. We report a case of 5q-syndrome following a MGUS IgMk with mutation of MYD88 L256P.

Lymphoid enhancer binding factor-1 (LEF1) expression as a prognostic factor in adult acute promyelocytic leukemia.

Lymphoid enhancer-binding factor 1 (LEF1) is a downstream effector of the Wnt/ β-catenin signaling pathway. High LEF1 expression has been reported as a prognostic marker in hematologic malignancies. We evaluated the prognostic significance of LEF1 expression in 78 adult acute promyelocytic leukemia (APL) patients.

Acute myeloid leukemia with t(16;16) (p13;q22) showing a new CBFB-MYH11 fusion transcript associated with an atypical leukemic blasts morphology.

Acute myeloid leukemia (AML) cases with inv(16)(p13q22) or t(16;16)(p13;q22) are characterized by multiple CBFB-MYH11 fusion transcripts, type A being the most frequent. Rare fusion variants are frequently correlated with an atypical cytomorphology, but their biologic and prognostic significance is unclear. We report a case of acute myeloid leukemia with a balanced t(16;16)(p13;q22) and additional monosomy 13 showing a new CBFB-MYH11 fusion transcript variant.

Analysis of copy number variations among diverse cattle breeds.

Genomic structural variation is an important and abundant source of genetic and phenotypic variation. Here, we describe the first systematic and genome-wide analysis of copy number variations (CNVs) in modern domesticated cattle using array comparative genomic hybridization (array CGH), quantitative PCR (qPCR), and fluorescent in situ hybridization (FISH). The array CGH panel included 90 animals from 11 Bos taurus, three Bos indicus, and three composite breeds for beef, dairy, or dual purpose.

Analysis of recent segmental duplications in the bovine genome.

Background: Duplicated sequences are an important source of gene innovation and structural variation within mammalian genomes. We performed the first systematic and genome-wide analysis of segmental duplications in the modern domesticated cattle (Bos taurus). Using two distinct computational analyses, we estimated that 3.

Evolutionary formation of new centromeres in macaque.

A systematic fluorescence in situ hybridization comparison of macaque and human synteny organization disclosed five additional macaque evolutionary new centromeres (ENCs) for a total of nine ENCs. To understand the dynamics of ENC formation and progression, we compared the ENC of macaque chromosome 4 with the human orthologous region, at 6q24.3, that conserves the ancestral genomic organization.