Chromosome Breakage Hotspots and Delineation of the Critical Region for the 9p-Deletion Syndrome

Abstract

The clinical features of the 9p-deletion syndrome include dysmorphic facial features (trigonocephaly, midface hypoplasia, upward-slanting palpebral fissures, and a long philtrum) and mental retardation. The majority of these patients appear to have similar cytogenetic breakpoints in 9p22, but some cases show phenotypic heterogeneity. To define the breakpoints of the deleted chromosomes, we studied 24 patients with a deletion of 9p, by high-resolution cytogenetics, FISH with 19 YACs, and PCR using 25 different sequence-tagged sites. Of 10 different breakpoints identified, 9 were localized within an approximately 5-Mb region, in 9p22-p23, that encompasses the interval between D9S1869 (telomeric) and D9S162 (centromeric). Eight unrelated patients had a breakpoint (group 1) in the same interval, between D9S274 (948h1) and D9S285 (767f2), suggesting a chromosome-breakage hotspot. Among 12 patients, seven different breakpoints (groups 3-9) were localized to a 2-Mb genomic region between D9S1709 and D9S162, which identified a breakpoint-cluster region. The critical region for the 9p-deletion syndrome maps to a 4-6-Mb region in 9p22-p23. The results from this study have provided insight into both the heterogeneous nature of the breakage in this deletion syndrome and the resultant phenotype-karyotype correlations.

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

“…The phenotypes observed in this case were consistent with those of other previously reported patient with 9p deletion syndrome 6,7,12) . In addition, our patient showed symptoms of AMC, which have not previously been reported in patients with de novo 9p deletion syndrome.…”

“…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) . CER1…”

“…The gonadal phenotype appears in the form of complete gonadal dysgenesis, hypospadias, cryptorchidism, and/or gonadoblastoma 7,8) .…”

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

“…This 9p24.3 critical region is included in the deletion of our patient, who only shows bilateral cryptorchidism, a mild genital/ gonadal phenotype. Different critical regions have been suggested for the consensus phenotype associated to 9p deletion syndrome (Christ et al, 1999;Faas et al, 2007;Kawara et al, 2006;Swinkles et al, 2008). The first, proposed in 1999 (Christ et al, 1999) is associated with developmental delay/mental retardation, trigonocephaly, midface hypoplasia and long philtrum.…”

“…In addition, 9p deletion carriers show variable genital and/or gonadal disorders if XY patients, trigonocephaly, midface hypoplasia, small and up slanting palpebral fissures, long philtrum (Christ et al, 1999;Kawara et al, 2006;Swinkles et al, 2008). Conversely 9p duplication carriers present with microcephaly/ brachycephaly, down slanting palpebral fissures, bulbous nasal tip, short philtrum and short neck (Fujimoto et al, 1998;Jelin et al, 2010;Zou et al, 2009).…”