Case Report: Neuroblastoma Breakpoint Family Genes Associate With 1q21 Copy Number Variation Disorders

Microduplications and reciprocal microdeletions of chromosome 1q21. 1 and/or 1q21.2 have been linked to variable clinical features, but the underlying pathogenic gene(s) remain unclear. Here we report that distinct microduplications were detected on chromosome 1q21.2 (GRCh37/hg19) in a mother (255 kb in size) and her newborn daughter (443 kb in size), while the same paternal locus was wild-type. Although the two microduplications largely overlap in genomic sequence (183 kb overlapping), the mother showed no clinical phenotype while the daughter presented with several features that are commonly observed on 1q21 microduplication or microdeletion patients, including developmental delay, craniofacial dysmorphism, congenital heart disease and sensorineural hearing loss. NBPF15 and NBPF16, two involved genes that are exclusively duplicated in the proband, may be the cause of the clinical manifestations. This study supports an association between NBPF genes and 1q21 copy number variation disorders.

Chromosome 1q21 abnormalities in multiple myeloma

Gain of chromosome 1q (+1q) is one of the most common recurrent cytogenetic abnormalities in multiple myeloma (MM), occurring in approximately 40% of newly diagnosed cases. Although it is often considered a poor prognostic marker in MM, +1q has not been uniformly adopted as a high-risk cytogenetic abnormality in guidelines. Controversy exists regarding the importance of copy number, as well as whether +1q is itself a driver of poor outcomes or merely a common passenger genetic abnormality in biologically unstable disease. Although the identification of a clear pathogenic mechanism from +1q remains elusive, many genes at the 1q21 locus have been proposed to cause early progression and resistance to anti-myeloma therapy. The plethora of potential drivers suggests that +1q is not only a causative factor or poor outcomes in MM but may be targetable and/or predictive of response to novel therapies. This review will summarize our current understanding of the pathogenesis of +1q in plasma cell neoplasms, the impact of 1q copy number, identify potential genetic drivers of poor outcomes within this subset, and attempt to clarify its clinical significance and implications for the management of patients with multiple myeloma.

Epidermal Proliferation and Differentiation in Ichthyosis Vulgaris

A B S T R A C TEpidermal proliferation and differentiation is a physiological process which playscrucial role in protecting human body from external environment. Ichthyosisvulgaris is a disease caused by disruption of epidermal differentiation process.Disrupted of profilaggrin conversion to filaggrin caused by mutations from thefilaggrin gene (FLG) located on chromosome 1q21. Recently, caused of ichthyosisvulgaris is mutation of the CASP14 gene on chromosome 19p13.12 which producescaspase-14, is involved in the proteolytic degradation of filaggrin. Clinicalmanifestations of ichthyosis vulgaris are hyperlinear palmar and plantar, keratosispilaris, xerosis, and localized or generalized scaling of the skin. Application ofemollients, humectants and keratolytic agents are the main treatment of ichthyosisvulgaris. Further research on caspase-14 as a therapeutic target is needed in thetreatment of ichthyosis vulgaris.

Diagnostic challenges in pyruvate kinase deficiency

Red cell pyruvate kinase deficiency is a rare congenital, nonspherocytic hemolytic anemia caused by a glycolytic defect that is due to compound heterozygous or homozygous mutations in the PKLR gene on chromosome 1q21. The article presents analytical review of literature and the clinical case of pyruvate kinase deficiency. Patient's parents agreed to use personal dats and photos in research and publications.

Further Clinical Delineation of Chromosome 1q21Microduplication Syndrome: Robin Sequence as an Under-Recognized Association in Chromosomal Microdeletions and Duplications

Robin sequence (RS) has been reported in association with single gene disorders and chromosomal abnormalities; however, it has not previously been described in connection with chromosome 1q21 microduplication. We present the first known case of a neonate diagnosed with chromosome 1q21.1 microduplication syndrome and RS requiring surgical airway intervention. This case demonstrates the value of genetic testing in cases of RS presenting with other congenital anomalies.

ADAR1 can drive Multiple Myeloma progression by acting both as an RNA editor of specific transcripts and as a DNA mutator of their cognate genes

ABSTRACTRNA editing is an epitranscriptomic modification of emerging relevance to disease development and manifestations. ADAR1, which resides on human chromosome 1q21, is an RNA editor whose over-expression, either by interferon (IFN) induction or through gene amplification, is associated with increased editing and poor outcomes in Multiple Myeloma (MM). Here we explored the role of ADAR1 in the context of MM progression, by focusing on a group of 23 patients in the MMRF CoMMpass Study for which RNAseq and WES datasets exist for matched pre-and post-relapse samples. Our analysis reveals an acquisition of new DNA mutations on disease progression at specific loci surrounding the sites of ADAR associated (A-to-I) RNA editing. These analyses suggest that the RNA editing enzyme ADAR1 can function as a DNA mutator during Multiple Myeloma (MM) progression, and further imply that guide-targeted RNA editing has the capacity to generate specific mutational signatures at predetermined locations. This dual role of RNA editor and DNA mutator might be shared by other deaminases, such as APOBECs, so that DNA mutation might be the result of collateral damage on the genome by an editing enzyme whose primary job is to re-code the cognate transcript toward specific functional outcomes.