miRNA target prediction of avian Z-linked DMRT1 gene during sex determination in chicken (G. Gallus)

Sex determination in dimorphic animal, such as chicken (G. Gallus), is controlled by the expression of doublesex and mab-3 related transcription factor 1 (DMRT1) gene. This gene act as sex determination switch by critically needed for testis differentiation and as antagonist of ovarian development. miRNA, is belongs to short noncoding RNA which modulate gene expression in specific or board targeted genes. This study was aimed to predict miRNA(s) candidate targeted to DMRT1 expression in chicken. In silico method was employed to mining miRNA targeted to DMRT1 using three online databases namely miRDB, TargetScan, and microT-CDS. Following prediction, clustering was performed to select common miRNA(s) in minimal two databases for gene ontology (GO) analysis. Totally 78 miRNAs were targeted to DMRT1 3’UTR, and eight miRNA(s) were found in minimal two databases. The GO analysis found seven distinct biological functions in membrane, cytoplasm, protein binding, nucleus, integral component of membrane and molecular function, and all are related to the cell growth namely cell proliferation. According to the result, it shows the possibility to use selected candidate of miRNA(s) targeted to DMRT1 to reveal the sex determination mechanism at early stage of chicken development.

Homozygous DMRT1 mutation c.967G>A found in a Chinese patient with 46,XY complete gonadal dysgenesis and review of literature

A Chinese woman with 46,XY CGD was diagnosed by clinicopathologic findings . A homozygous mutation c.967G>A(p. Val323Ile) in the DMRT1 gene was detected in the patient by WES. As far as we know, this is the first case of 46,XY CGD caused by a homozygous mutation in the DMRT1 gene.

EARLY-ONSET GONADOBLASTOMA IN A 13-MONTH-OLD INFANT WITH 46,XY COMPLETE GONADAL DYSGENESIS IDENTIFIED WITH PRENATAL TESTING: A CASE OF CHROMOSOME 9p DELETION

Objective: Individuals with 46,XY complete gonadal dysgenesis (CGD) are at high risk of developing gonadal neoplasms. Chromosome 9p monosomy with deletion of the DMRT1 gene, a key transcription factor in testicular development, is one of the known causes of 46,XY CGD. Noninvasive prenatal testing (NIPT) is being increasingly used, and can identify disorders of sexual development (DSDs). Methods: We report the case of a 46,XY infant with phenotypically female external genitalia, müllerian structures including uterus and fallopian tubes, and bilateral streak gonads who was found to have unilateral gonadoblastoma at 13 months. 46,XY DSD was suggested prenatally when discordance between NIPT and fetal ultrasound was noted. Results: Genetic investigation revealed a deletion of 12.5 million base pairs at chromosome 9p24.3, which includes the doublesex and MAB-3-related transcription factor-1 ( DMRT1) gene. Conclusion: Current guidelines recommend gonadectomy at the time of diagnosis in cases of 46,XY CGD, and our patient had gonadoblastoma at 13 months. 46,XY DSD, including rare disorders such as CGD, will be increasingly identified before birth with more widespread use of NIPT, raising the question about the appropriate timing of gonadectomy in prenatal diagnoses. Our case supports the current recommendation to perform gonadectomy as early as possible after diagnosis.