Three patients with terminal deletions within the subtelomeric region of chromosome 9q

Abstract

We report on three male infants with de novo terminal deletions of chromosome 9q34.3. The clinical features are compared to the nine cases described in the literature. Case 1 and 3 were ascertained following the use of subtelomeric FISH to screen for a chromosomal anomaly, case 2 was confirmed by FISH probe following detection of a 9q deletion on standard karyotyping. Deletions in this region result in severe developmental delay, a distinct facial phenotype, cardiac anomalies, obesity, and respiratory failure, which may result in premature death. The delineation of the 9q deletion phenotype will aid diagnosis and genetic counseling as subtelomere FISH screening becomes more widely available.

Purine-mediated signalling triggers eye development

“…Human eye and brain development may also depend on ENTPDase2 activity: spontaneous mutations at 9q34, the region bearing the locus of the E-NTPDase2 gene, consistently give head and brain abnormalities that include a range of eye defects including microphthalmia, analogous to the phenotypes we have reported in the frog [15][16][17][18] . Our studies raise several fascinating questions such as the identity of the ATP-releasing cells and the chain of events that connect activation of the P2Y1 receptor in the mesoderm/endoderm to initiation of EFTF expression in the ectoderm.…”

“…We next measured ATP release [12][13][14] in the presumptive eye field, demonstrating a transient release of ATP at a time that could plausibly trigger (once converted to ADP) expression of the EFTFs. This surprising role for transient purinemediated signalling in eye development may be widely conserved, because alterations to the locus of E-NTPDase2 on human chromosome 9 cause severe head and eye defects, including microphthalmia [15][16][17][18] . Our results suggest a new mechanism for the initiation of eye development.…”

Update on Kleefstra Syndrome

“…Patient 4 suffered from central apnea and patient 7 and 10 had respiratory problems secondary to a viral bronchiolitis and aspiration, respectively. Central apnea has been reported in 1 previously published patient who had a cytogenetically visible deletion [Neas et al, 2005]. From a personal communication we know an additional patient with central apnea who has a 9q subtelomeric deletion of more than 3 Mb as well.…”

“…The majority of the deletions described here (11/16) were identified by genome-wide array analysis. A large number of previous deletions were reported before genomewide array platforms became common use in routine diagnostic settings, and were either detected by routine FISH or MLPA [Dawson et al, 2002;Cormier-Daire et al, 2003;Font-Montgomery et al, 2004;Iwakoshi et al, 2004;Neas et al, 2005]. Some studies reported fine-mapping of deletions with additional specific 9q probes Stewart et al, 2004].…”

“…The syndrome is either caused by a submicroscopic deletion in the chromosomal region 9q34.3 or an intragenic mutation of the euchromatin histone methyltransferase 1 (EHMT1) gene causing haploinsufficiency of EHMT1 . So far, 85 patients, including 75 patients with a 9q34.3 deletion and 10 patients with an EHMT1 mutation, have been reported [Schimmenti et al, 1994;Ayyash et al, 1997;Dawson et al, 2002;Cormier-Daire et al, 2003;Font-Montgomery et al, 2004;Harada et al, 2004;Iwakoshi et al, 2004;Stewart et al, 2004;Neas et al, 2005;Yatsenko et al, 2005Yatsenko et al, , 2009Kleefstra et al, 2006aKleefstra et al, , b, 2009Stewart and Kleefstra, 2007;Verhoeven et al, 2010;Willemsen et al, 2011]. EHMT1 encodes a histone H3 Lys 9 methyltransferase and is thereby involved in chromatin remodeling [Ogawa et al, 2002].…”