BackgroundThe premature fusion of metopic sutures results in the clinical phenotype of trigonocephaly. An association of this characteristic with the monosomy 9p syndrome is well established and the receptor-type protein tyrosine phosphatase gene (PTPRD), located in the 9p24.1p23 region and encoding a major component of the excitatory and inhibitory synaptic organization, is considered as a good candidate to be responsible for this form of craniosynostosis. Moreover PTPRD is known to recruit multiple postsynaptic partners such as IL1RAPL1 which gene alterations lead to non syndromic intellectual disability (ID).ResultsWe describe a 30 month old boy with severe intellectual disability, trigonocephaly and dysmorphic facial features such as a midface hypoplasia, a flat nose, a depressed nasal bridge, hypertelorism, a long philtrum and a drooping mouth.Microarray chromosomal analysis revealed the presence of a homozygous deletion involving the PTPRD gene, located on chromosome 9p22.3. Reverse Transcription PCR (RT-PCR) amplifications all along the gene failed to amplify the patient's cDNA in fibroblasts, indicating the presence of two null PTPRD alleles.Synaptic PTPRD interacts with IL1RAPL1 which defects have been associated with intellectual disability (ID) and autism spectrum disorder. The absence of the PTPRD transcript leads to a decrease in the expression of IL1RAPL1. These results suggest the direct involvement of PTPRD in ID, which is consistent with the PTPRD -/- mice phenotype.Deletions of PTPRD have been previously suggested as a cause of trigonocephaly in patients with monosomy 9p and genome-wide association study suggested variations in PTPRD are associated with hearing loss.ConclusionsThe deletion identified in the reported patient supports previous hypotheses on its function in ID and hearing loss. However, its involvement in the occurrence of metopic synostosis is still to be discussed as more investigation of patients with the 9p monosomy syndrome is required.
BackgroundThe premature fusion of metopic sutures results in the clinical phenotype of trigonocephaly. An association of this characteristic with the monosomy 9p syndrome is well established and the receptor-type protein tyrosine phosphatase gene (PTPRD), located in the 9p24.1p23 region and encoding a major component of the excitatory and inhibitory synaptic organization, is considered as a good candidate to be responsible for this form of craniosynostosis. Moreover PTPRD is known to recruit multiple postsynaptic partners such as IL1RAPL1 which gene alterations lead to non syndromic intellectual disability (ID).ResultsWe describe a 30 month old boy with severe intellectual disability, trigonocephaly and dysmorphic facial features such as a midface hypoplasia, a flat nose, a depressed nasal bridge, hypertelorism, a long philtrum and a drooping mouth.Microarray chromosomal analysis revealed the presence of a homozygous deletion involving the PTPRD gene, located on chromosome 9p22.3. Reverse Transcription PCR (RT-PCR) amplifications all along the gene failed to amplify the patient's cDNA in fibroblasts, indicating the presence of two null PTPRD alleles.Synaptic PTPRD interacts with IL1RAPL1 which defects have been associated with intellectual disability (ID) and autism spectrum disorder. The absence of the PTPRD transcript leads to a decrease in the expression of IL1RAPL1. These results suggest the direct involvement of PTPRD in ID, which is consistent with the PTPRD -/- mice phenotype.Deletions of PTPRD have been previously suggested as a cause of trigonocephaly in patients with monosomy 9p and genome-wide association study suggested variations in PTPRD are associated with hearing loss.ConclusionsThe deletion identified in the reported patient supports previous hypotheses on its function in ID and hearing loss. However, its involvement in the occurrence of metopic synostosis is still to be discussed as more investigation of patients with the 9p monosomy syndrome is required.
“…2008; Swinkels et al. 2008; Shimojima and Yamamoto 2009). Although, along with these works, some genes such as CER1 , TYRP1 and PTPRD have been postulated as possible candidate genes, no gene has yet been identified as conclusively responsible for the syndrome (Shimojima and Yamamoto 2009).…”
Section: Discussionmentioning
confidence: 99%
“…2008; Swinkels et al. 2008; Shimojima and Yamamoto 2009). Here, we describe a patient with a terminal 9p deletion of approximately 9 Mb who has the typical clinical manifestations of 9p monosomy syndrome, including trigonocephaly and sex reversal.…”
We describe a patient with typical manifestations of 9p monosomy syndrome, including trigonocephaly and sex reversal. Array comparative genomic hybridization (CGH) revealed a 9p terminal deletion of approximately 9 Mb with the breakpoint at 9p23. We compared the deleted segments of 9p associated with reported cases of 9p monosomy syndrome with trigonocephaly. We did not identify a region that was shared by all patients; however, when only pure terminal or interstitial deletions that did not involve material from any other chromosome were compared, we identified a segment from D9S912 to RP11-439I6 of approximately 1 Mb that was deleted in every patient. We propose that this 1-Mb segment might be the critical region for 9p monosomy syndrome with trigonocephaly.
“…Swinkels et al [2008] have identified a 300 Kb region responsible for the 9p syndrome phenotype, including trigonocephaly, between 15.1 and 15.4 Mb from the telomere. Of note, trigonocephaly has been reported in patients with smaller deletions of 9p not extending to the region described by Swinkels [Muroya et al, 2000;Hauge et al, 2008;Barbaro et al, 2009;Shimojima and Yamamoto, 2009], thus suggesting that other genes or factors mapping distally to this critical region may be involved. Shimojima and Yamamoto [2009] identified a second putative critical region for trigonocephaly, located distally to the region defined by Swinkles, related to deletion of the PTPRD gene.…”
Section: To the Editormentioning
confidence: 95%
“…Of note, trigonocephaly has been reported in patients with smaller deletions of 9p not extending to the region described by Swinkels [Muroya et al, 2000;Hauge et al, 2008;Barbaro et al, 2009;Shimojima and Yamamoto, 2009], thus suggesting that other genes or factors mapping distally to this critical region may be involved. Shimojima and Yamamoto [2009] identified a second putative critical region for trigonocephaly, located distally to the region defined by Swinkles, related to deletion of the PTPRD gene. PTPRD is a 45-exon gene encoding for a member of the protein tyrosine phosphatase (PTP) family and located in the 9p24.1-p23 region (8,304,602,505).…”
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