We report a unique pediatric case of hypergranular acute myeloid leukemia with myelodysplasia-related changes. The patient presented with moderate leukocytosis with neutrophilia with left-shift maturation and dysplasia, anemia, and multiple sclerotic bone lesions. The bone marrow was hypercellular with a predominance of myeloblast cells and/or abnormal promyelocytes with hypergranular cytoplasm. Flow cytometric immunophenotyping showed that the leukemic cells were positive for CD13, CD33, and myeloperoxidase, and negative for HLA-DR and CD34. Morphology and immunophenotyping were highly suggestive of acute promyelocytic leukemia. The classic t(15;17) or other RAR? rearrangements were not detected by cytogenetic or molecular assays, ruling out acute promyelocytic leukemia. Standard cytogenetic analysis showed that the karyotype of the predominant clone was 47,XY,+6 with evidence of clonal evolution to 47,XY,+6,del(5)(q22q33). A literature and database review showed that trisomy 6 is a rare occurrence in hematological malignancies and, to our knowledge, has never been reported in association with del(5)(q22q33) in a child presenting with hypergranular acute myeloid leukemia with myelodysplasia-related changes. We present a current review of the literature and summarize the clinical features of 57 cases of trisomy 6 as the primary chromosomal abnormality in hematological disease.
We report on a patient with severe intellectual disability, microcephaly, short stature, and dysmorphic features who, based on standard karyotyping, has two cytogenetic abnormalities: an apparently balanced paracentric inversion of chromosome 7, inv(7)(q31.2q36), and a small supernumerary ring chromosome derived entirely of material from chromosome 19. While the inversion was detected in all cells, mosaicism was observed for the ring chromosome. Interestingly, apparently identical cytogenetic abnormalities were detected in the patients mother, who presented with normal stature, few dysmorphic features, and normal cognition without microcephaly. While the level of mosaicism could not adequately explain the phenotypic discordance, comparative genome hybridization revealed a de novo terminal deletion of chromosome 7, del(7)(q36.2), and a terminal duplication of chromosome 7, dup(7)(p22.1) in the patient. Additional cytogenetic investigation revealed that the patient inherited a recombinant chromosome derived from a cryptic maternal pericentric inversion: inv(7)(p22q36). The patients distinctive features are consistent with the wide phenotypic spectrum reported in 7p duplication and 7q terminal deletion syndromes. These chromosomal regions contain several candidate genes of clinical significance, including SHH, EN2, and FAM20C. Our findings strongly suggest that our patients phenotype is largely attributable to partial 7pter trisomy and partial 7qter monosomy rather than mosaic supernumerary ring chromosome 19.
To determine the detection rate of clinically significant chromosome abnormalities using quantitative fluorescent polymerase chain reaction (QF-PCR) of fetal DNA in comparison with G-banded analysis of cultured amniotic fluid cells and determine the residual risk if QF-PCR were performed alone for low-risk cases.
Nablus mask-like facial syndrome (NMLFS) has many distinctive phenotypic features, particularly tight glistening skin with reduced facial expression, blepharophimosis, telecanthus, bulky nasal tip, abnormal external ear architecture, upswept frontal hairline, and sparse eyebrows. Over the last few years, several individuals with NMLFS have been reported to have a microdeletion of 8q21.3q22.1, demonstrated by microarray analysis. The minimal overlapping region is 93.98-96.22?Mb (hg19). Here we present clinical and microarray data from five singletons and two mother-child pairs who have heterozygous deletions significantly overlapping the region associated with NMLFS. Notably, while one mother and child were said to have mild tightening of facial skin, none of these individuals exhibited reduced facial expression or the classical facial phenotype of NMLFS. These findings indicate that deletion of the 8q21.3q22.1 region is necessary but not sufficient for development of the NMLFS. We discuss possible genetic mechanisms underlying the complex pattern of inheritance for this condition.
We report on a girl with trisomy 12 mosaicism diagnosed postnatally. She has been followed from 4 months of age for developmental delay, unilateral sensorineural hearing loss, intestinal malrotation, hemi-hyperplasia, pigmentary dysplasia, retinopathy, and a vascular ring. To our knowledge, there have been no reports of complete trisomy 12 in the literature. However there have been a few reports describing the phenotype of individuals with trisomy 12 mosaicism. This case report is a description of the eighth liveborn individual diagnosed postnatally with this condition.
Pericentric chromosome inversions are often associated with infertility, recurrent pregnancy loss, and an increased risk for offspring with congenital anomalies. We report on a chromosome 1 inversion between 1p36.21 and 1q42.13, one of the largest described familial pericentric inversions of chromosome 1. The inversion was ascertained following the birth of a female with multiple congenital anomalies due to a recombinant chromosome 1. The inversion was subsequently detected or inferred in 16 healthy individuals over five generations. Interestingly, with a ratio of 16 carriers to 6 noncarriers, there appears to be transmission distortion of the inverted chromosome 1 within the family. Although there is no reported difficulty conceiving in the family, the risk of miscarriage is higher than predicted at 34% (13/38). The recurrence risk of a recombinant chromosome also appears to be lower than expected based on the mode of ascertainment. This case contributes to the spectrum of clinical features of chromosome 1 recombinants and raises the question of whether or not there is a selective advantage of the inverted chromosome at meiosis, conception, or post-zygotically that has contributed to transmission distortion of the inverted chromosome.
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