Characterization of deletions at 9p affecting the candidate regions for sex reversal and deletion 9p syndrome by MLPA

Abstract

The distal region on the short arm of chromosome 9 is of special interest for scientists interested in sex development as well as in the clinical phenotype of patients with the 9p deletion syndrome, characterized by mental retardation, trigonocephaly and other dysmorphic features. Specific genes responsible for different aspects of the phenotype have not been identified. Distal 9p deletions have also been reported in patients with 46,XY sex reversal, with or without 9p deletion syndrome. Within this region the strongest candidates for the gonadal dysgenesis phenotype are the DMRT genes; however, the genetic mechanism is not clear yet. Multiple ligation-dependent probe amplification represents a useful technique to evaluate submicroscopic interstitial or distal deletions that would help the definition of the minimal sex reversal region on 9p and could lead to the identification of gene(s) responsible of the 46,XY gonadal disorders of sex development (DSD). We designed a synthetic probe set that targets genes within the 9p23-9p24.3 region and analyzed a group of XY patients with impaired gonadal development. We characterized a deletion distal to the DMRT genes in a patient with isolated 46,XY gonadal DSD and narrowed down the breakpoint in a patient with a 46,XY del(9)(p23) karyotype with gonadal DSD and mild symptoms of 9p deletion syndrome. The results are compared with other patients described in the literature, and new aspects of sex reversal and the 9p deletion syndrome candidate regions are discussed.

Complex rearrangement involving 9p deletion and duplication in a syndromic patient: Genotype/phenotype correlation and review of the literature

“…The phenotypes of the patients at comparison, each identified by his/her 9p rearrangement, are summarized in Table 2. With regard to 9p deletion syndrome a critical region involved in gonadal dysgenesis in XY patients has been proposed to reside at 9p24.3, from 9p telomere to the DMRT genes cluster (Barbaro et al, 2009;Ogata et al, 1997). The phenotype of XY patients with terminal 9p deletions varies from complete sex reversal to milder phenotypes.…”

Pathologic Genomic Rearrangements in Idiopathic Mentally Retarded Patients from Iran

“…Genes such as TACC3, LETM1 and FGFR3 which are involved in duplicated region may have roles in the patient phenotype such as Seizure and skeletal abnormalities [14][15][16][17][18]. As far as 9p deletion is concerned, patients with 9p deletion present with MR, craniofacial dysmorphic features and genital or gonadal disorders [19][20][21].…”

A Case of Partial Short Arm Deletion in Chromosome 9 with Inguinal Hernia, Testicular Cystic Lesion, and Arthrogryposis Multiplex Congenita

“…and 2, which are located on 9p24.3, and other genetic defects are likely associated with the abnormal sexual development 10) . DMRT1 activates testis specific genes such as Sox9 and Sox8, and represses ovary specific genes encoding Fox12, Wnt4 and R spondin 1 signaling proteins, and estrogen receptors 2,5,7) .…”

“…Abnormal muscle tone, mainly hypohonia, has been observed in some patients with the 9p24 deletion syndrome 10) . However, arthrogryposis multiplex congenita (AMC) has not been reported in any case of 9p24 deletion.…”