Role of SNAP29, LZTR1 and P2RXL1 genes on immune regulation in a patient with atypical 0.5Mb deletion in 22q11.2 region

Soares, Diogo Cordeiro de Queiroz; Dutra, Roberta Lelis; Quaio, Caio Robledo; Melaragno, Maria Isabel; Kulikowski, Leslie Domenici; Torres, Leuridan Cavalcante; Kim, Chong

doi:10.1016/j.clim.2012.07.013

Cited by 6 publications

(6 citation statements)

References 8 publications

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“…Among the 19 genes (20 probes; TBX1 had two probes: TBX1-2 and TBX1-7 ) that had deletions or amplifications in the 22q11.2 region found in this study, seven of them had higher frequency (deletions or amplifications in six or more patients) and have been previously reported to be related to the phenotypes of the 22q11.2 syndrome. Among these seven genes, there were six genes that had deletions ( CDC45 ,16 23 TBX1 ,24 25 USP18 ,26 RTDR1 ,27 ZNF74 28 and SNAP29 ),29 30 and one gene ( TOP3B 31) had amplification. Figure 2D shows the quantity of patients according to the number of deleted genes.…”

Section: Resultsmentioning

confidence: 99%

Genetic characterisation of 22q11.2 variations and prevalence in patients with congenital heart disease

et al. 2019

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ObjectivesThe 22q11.2 deletion syndrome is considered the most frequent chromosomal microdeletion syndrome in humans and the second leading chromosomal cause of congenital heart disease (CHD). We aimed to identify the prevalence and the detailed genetic characterisation of 22q11.2 region in children with CHD including simple defects and to explore the genotype-phenotype relationship between deletion/amplification type and clinical data.MethodsPatients with CHD for surgery were screened by multiplex ligation-dependent probe amplification and capillary electrophoresis methods. Universal Probe Library technology was applied for validation.ResultsIn 354 patients with CHD, 40 (11.3%) carried different levels of deletions/amplifications at the 22q11.2 region with various phenotypes. The affected genes at this region include CDC45 (15 patients), TBX1 (8), USP18 (8), RTDR1 (7), SNAP29 (6), TOP3B (6), ZNF74 (4) and other genes with less frequency. Among those, two patients carried 3 Mb typically deleted region from CLTCL1 to LZTR1 (low copy repeats A–D) or 1.5 Mb deletions from CLTCL1 to MED15 (low copy repeats A–C). Clinical facial manifestations were found in 12 patients.ConclusionsThis study revealed an unexpected high prevalence of chromosome 22q11.2 variations in patients with CHD even in simple defects. The genotype-phenotype relationship analysis suggests that genetic detection of 22q11.2 may become necessary in all patients with CHD and that detection of unique deletions or amplifications may provide useful insight into personalised management in patients with CHD.

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Section: Resultsmentioning

confidence: 99%

Genetic characterisation of 22q11.2 variations and prevalence in patients with congenital heart disease

et al. 2019

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“…None of the central 22q11.2 deletion carriers presented with hypocalcemia, hypoparathyroidism or a clinical phenotype of DiGeorge anomaly, but recurrent ear infections occurred in 17% of the patients, and a mild immunodeficiency with diminished number of T‐cells and increased number natural killer cells was reported in one patient of our cohort. Elevated natural killer cells and abnormal T cell subpopulations were also reported in one previous case [D'Angelo et al, ; de Queiroz Soares et al, ]. It has been suggested that the genes SNAP29 , LZTR1 , and/or P2RXL1 could be important for immune regulation [de Queiroz Soares et al, ].…”

Section: Discussionmentioning

confidence: 54%

“…Elevated natural killer cells and abnormal T cell subpopulations were also reported in one previous case [D'Angelo et al, ; de Queiroz Soares et al, ]. It has been suggested that the genes SNAP29 , LZTR1 , and/or P2RXL1 could be important for immune regulation [de Queiroz Soares et al, ].…”

Section: Discussionmentioning

confidence: 54%

Central 22q11.2 deletions

Rump

Leeuw

Essen

et al. 2014

American J of Med Genetics Pt A

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22q11.2 deletion syndrome is one of the most common microdeletion syndromes. Most patients have a deletion resulting from a recombination of low copy repeat blocks LCR22-A and LCR22-D. Loss of the TBX1 gene is considered the most important cause of the phenotype. A limited number of patients with smaller, overlapping deletions distal to the TBX1 locus have been described in the literature. In these patients, the CRKL gene is deleted. Haploinsufficiency of this gene has also been implicated in the pathogenesis of 22q11.2 deletion syndrome. To distinguish these deletions (comprising the LCR22-B to LCR22-D region) from the more distal 22q11.2 deletions (located beyond LCR22-D), we propose the term "central 22q11.2 deletions". In the present study we report on 27 new patients with such a deletion. Together with information on previously published cases, we review the clinical findings of 52 patients. The prevalence of congenital heart anomalies and the frequency of de novo deletions in patients with a central deletion are substantially lower than in patients with a common or distal 22q11.2 deletion. Renal and urinary tract malformations, developmental delays, cognitive impairments and behavioral problems seem to be equally frequent as in patients with a common deletion. None of the patients had a cleft palate. Patients with a deletion that also encompassed the MAPK1 gene, located just distal to LCR22-D, have a different and more severe phenotype, characterized by a higher prevalence of congenital heart anomalies, growth restriction and microcephaly. Our results further elucidate genotype-phenotype correlations in 22q11.2 deletion syndrome spectrum.

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“…However, since an atypical deletion that includes SNAP29, LZTR1 and P2RXL1 was recently found associated with immune deficiency, it remains possible that the mutations that we identified are responsible for this phenotype. 50 In conclusion, we have found that mutations in a single gene, in unrelated patients, contribute to the phenotype of patients with a microdeletion syndrome, implicating SNAP29 as a major modifier of variable expressivity in 22q11.2DS patients. Our work confirms that the phenotypic variability observed in patients with 22q11.2DS may be due to additional mutations on the non-deleted chromosome, which in some instances unmask a previously described autosomal recessive condition such as the CEDNIK and potentially Kousseff syndromes, and in other cases simply contributes to the presence of atypical findings.…”

Section: Discussionmentioning

confidence: 69%

Hemizygous mutations in SNAP29 unmask autosomal recessive conditions and contribute to atypical findings in patients with 22q11.2DS

et al. 2012

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Background22q11.2 deletion syndrome (22q11.2DS) is the most common microdeletion disorder, affecting an estimated 1 : 2000–4000 live births. Patients with 22q11.2DS have a broad spectrum of phenotypic abnormalities which generally includes congenital cardiac abnormalities, palatal anomalies, and immunodeficiency. Additional findings, such as skeletal anomalies and autoimmune disorders, can confer significant morbidity in a subset of patients. 22q11.2DS is a contiguous gene DS and over 40 genes are deleted in patients; thus deletion of several genes within this region contributes to the clinical features. Mutations outside or on the remaining 22q11.2 allele are also known to modify the phenotype.MethodsWe utilised whole exome, targeted exome and/or Sanger sequencing to examine the genome of 17 patients with 22q11.2 deletions and phenotypic features found in <10% of affected individuals.Results and conclusionsIn four unrelated patients, we identified three novel mutations in SNAP29, the gene implicated in the autosomal recessive condition cerebral dysgenesis, neuropathy, ichthyosis and keratoderma (CEDNIK). SNAP29 maps to 22q11.2 and encodes a soluble SNARE protein that is predicted to mediate vesicle fusion at the endoplasmic reticulum or Golgi membranes. This work confirms that the phenotypic variability observed in a subset of patients with 22q11.2DS is due to mutations on the non-deleted chromosome, which leads to unmasking of autosomal recessive conditions such as CEDNIK, Kousseff, and a potentially autosomal recessive form of Opitz G/BBB syndrome. Furthermore, our work implicates SNAP29 as a major modifier of variable expressivity in 22q11.2 DS patients.

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Role of SNAP29, LZTR1 and P2RXL1 genes on immune regulation in a patient with atypical 0.5Mb deletion in 22q11.2 region

Cited by 6 publications

References 8 publications

Genetic characterisation of 22q11.2 variations and prevalence in patients with congenital heart disease

Genetic characterisation of 22q11.2 variations and prevalence in patients with congenital heart disease

Central 22q11.2 deletions

Hemizygous mutations in SNAP29 unmask autosomal recessive conditions and contribute to atypical findings in patients with 22q11.2DS

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