Ring chromosome 18 in combination with 18q12.1 (DTNA) interstitial microdeletion in a patient with multiple congenital defects

Abstract

BackgroundRing chromosome 18 [r(18)] syndrome represents a relatively rare condition with a complex clinical picture including multiple congenital dysmorphia and varying degrees of mental retardation. The condition is cytogenetically characterized by a complete or mosaic form of ring chromosome 18, with ring formation being usually accompanied by the partial loss of both chromosomal arms. Here we observed a 20-year-old male patient who along with the features typical for r(18) carriers additionally manifested a severe congenital subaortic stenosis. To define the genetic basis of such a compound phenotype, standard cytogenetic and high-resolution molecular-cytogenetic analysis of the patient was performed.Case presentationStandard chromosome analysis of cultured lymphocytes confirmed 46, XY, r(18) karyotype. Array-based comparative genomic hybridization (array-CGH) allowed to define precisely the breakpoints of 18p and 18q terminal deletions, thus identifying the hemizygosity extent, and to reveal an additional duplication adjoining the breakpoint of the 18p deletion. Apart from the terminal imbalances, we found an interstitial microdeletion of 442 kb in size (18q12.1) that encompassed DTNA gene encoding α-dystrobrevin, a member of dystrophin-associated glycoprotein complex. While limited data on the role of DTNA missense mutations in pathogenesis of human cardiac abnormalities exist, a microdeletion corresponding to whole DTNA sequence and not involving other genes has not been earlier described.ConclusionsA detailed molecular-cytogenetic characterization of the patient with multiple congenital abnormalities enabled to unravel a combination of genetic defects, namely, a ring chromosome 18 with terminal imbalances and DTNA whole-gene deletion. We suggest that such combination could contribute to the complex phenotype. The findings obtained allow to extend the knowledge of the role of DTNA haploinsufficiency in congenital heart malformation, though further comprehensive functional studies are required.Electronic supplementary materialThe online version of this article (doi:10.1186/s13039-016-0229-9) contains supplementary material, which is available to authorized users.

A microarray expression profile and bioinformatic analysis of circular RNA in human esophageal carcinoma

“…This circRNA is an exonic circRNA and is located on chr18 from 32386182 to 32392077, which is annotated as hsa_circ_0108310 in circBase, and its gene symbol is dystrobrevin alpha (DTNA). This gene encodes a cytoskeleton-interacting membrane protein that is involved in the formation and stability of synapses in the permeability of the blood-brain barrier and may be related to congenital heart malformation (38,39). However, the role of hsa_ circRNA_401955 in cancer has not been studied.…”

Genome‐wide DNA methylation analysis of Hashimoto's thyroiditis during pregnancy

“…In addition, the results of the present study showed that the DTNA gene was the seed gene of the functional epigenetic modules, suggesting an important role of this gene in the development of HT. The DTNA gene encodes α‐dystrobrevin, a member of the dystrophin‐associated glycoprotein complex, which has been associated with movement disorders, such as Duchenne muscular dystrophy [31]. Collins et al .…”

“…The DTNA gene encodes α-dystrobrevin, a member of the dystrophin-associated glycoprotein complex, which has been associated with movement disorders, such as Duchenne muscular dystrophy [31]. Collins et al demonstrated that the expression level of dystroglycan in the thyroid is regulated by thyroid-stimulating hormone [7].…”

Нови Геномни Технологии При Диагностиката На Вродени Аномалии

“…Високата разделителна способност на микрочипова-та СГХ я прави основен метод на избор при детекцията на кандидат-районите за гени, отговорни за различни генетични заболявания [1]. В някои случаи с неясна етиология са открити фамилни микроструктурни аберации, предавани в небалансиран вид в поколението.…”