* 602679

PHOSPHATE CYTIDYLYLTRANSFERASE 2, ETHANOLAMINE; PCYT2


Alternative titles; symbols

CYTIDYLYLTRANSFERASE, CTP-PHOSPHOETHANOLAMINE; ET
ETHANOLAMINE-PHOSPHATE CYTIDYLYLTRANSFERASE


HGNC Approved Gene Symbol: PCYT2

Cytogenetic location: 17q25.3     Genomic coordinates (GRCh38): 17:81,900,958-81,911,399 (from NCBI)


Gene-Phenotype Relationships
Location Phenotype Phenotype
MIM number
Inheritance Phenotype
mapping key
17q25.3 Spastic paraplegia 82, autosomal recessive 618770 AR 3

TEXT

Description

Phosphatidylethanolamine (PtdEtn; PE) is a major membrane phospholipid in both prokaryotic and eukaryotic cells. In the PtdEtn biosynthetic pathway, the enzyme CTP-phosphoethanolamine cytidylyltransferase (ET; EC 2.7.7.14) catalyzes the formation of CDP-ethanolamine from ethanolamine (summary by Nakashima et al., 1997). PE is one of the most abundant membrane lipids and is particularly enriched in the brain, where it represents about 45% of the phospholipid fraction (summary by Vaz et al., 2019).


Cloning and Expression

Nakashima et al. (1997) found that the S. cerevisiae ECT1 gene encodes ET. By screening a human glioblastoma cDNA expression library for the ability to complement a yeast ect1 mutation, they identified a cDNA encoding ET, or PCYT2. Expression of PCYT2 in yeast ect1 mutants restored ET activity. The sequence of the predicted 389-amino acid PCYT2 protein is 36% identical to that of the yeast ECT1 gene product. Northern blot analysis revealed that PCYT2 is expressed as an approximately 2-kb mRNA in various tissues, with strongest expression in liver, heart, and skeletal muscle.

Vaz et al. (2019) noted that the PCYT2 gene encodes at least 12 transcripts. The most abundant protein, cited in the article as a 44-kD isoform in some places and as a 42-kD isoform in others, which could represent the catalytically active isoform b. There is also a 49-kD isoform, which likely represents the catalytically active isoform a.


Gene Structure

Vaz et al. (2019) stated that the PCYT2 gene contains 14 exons.


Mapping

Stumpf (2020) mapped the PCYT2 gene to chromosome 17q25.3 based on an alignment of the PCYT2 sequence (GenBank AY251539.1) with the genomic sequence (GRCh38).


Molecular Genetics

In 5 patients from 4 unrelated families with autosomal recessive spastic paraplegia-82 (SPG82; 618770), Vaz et al. (2019) identified homozygous or compound heterozygous mutations in the PCYT2 gene (602679.0001-602679.0003). The mutations, which were found by exome sequencing and confirmed by Sanger sequencing through different laboratories, segregated with the disorder in all families. Patient fibroblasts showed significantly decreased, but not absent, PCYT2 activity compared to controls; residual activity ranged from 15 to 20% of controls. Western blot analysis showed absence of the normal 49-kD protein, with variably decreased levels of the normally most abundant isoform. Detailed lipidomic studies of patient fibroblasts showed several abnormalities, including accumulation of phosphatidylcholine etherphospholipids (PC(O)), neutral lipid species, and neutral etherlipid species. There was also a decrease in PE(O) (PE etherphospholipids) and PE/PC plasmalogen species. Patient blood samples also showed an abnormal accumulation of PC(O) compared to controls. Since some of the lipid levels did not reach expected levels of change, the authors suggested compensatory biochemical pathways. In summary, Vaz et al. (2019) concluded that etherlipid homeostasis is critical for the development and function of the brain.

In a patient (case 1) with SPG82, Kaiyrzhanov et al. (2021) identified compound heterozygous mutations in the PCYT2 gene (602679.0004 and 602679.0005). The mutations were identified by whole-exome sequencing and confirmed by Sanger sequencing. Each parent was heterozygous for one of the mutations.


Animal Model

Fullerton et al. (2007) found that Pcyt2-null mouse embryos died after implantation, prior to embryonic day 8.5.

Vaz et al. (2019) found that knockdown of the pcyt2 ortholog in zebrafish resulted in significantly decreased survival, poor growth, and abnormal tail-fin morphology.

Christen et al. (2024) identified a c.4A-G transition (XM_038546296.1) in the PCYT2 gene, predicted to result in an ile2-to-val substitution, in 11 Saarlooswolfdogs with progressive retinal and neurologic degeneration. The mutation was identified by linkage analysis, whole-genome sequencing, and Sanger sequencing. Phenotypic features included progressive retinal atrophy in 9 dogs and owner-reported blindness in 2 dogs. All 11 dogs had gait abnormalities, hindlimb weakness, tremors, ataxia, and cognitive changes. Histopathologic examination in a deceased 63-month-old affected dog demonstrated brain and spinal cord white matter astrocyte abnormalities, gliosis, and dilation of myelin sheaths. Lipidomic analysis in plasma from affected dogs demonstrated a significant accumulation of lipid ethers. Analysis of the mutation in a cohort of 998 healthy Saarlooswolfdogs demonstrated a mutant allele frequency of 9.9%.


ALLELIC VARIANTS ( 5 Selected Examples):

.0001 SPASTIC PARAPLEGIA 82, AUTOSOMAL RECESSIVE

PCYT2, HIS244TYR
  
RCV001003406...

In a 5.5-year-old boy (patient 1), born of unrelated Hungarian parents, with autosomal recessive spastic paraplegia-82 (SPG82; 618770), Vaz et al. (2019) identified compound heterozygous missense mutations in the PCYT2 gene: a c.920C-T transition (c.920C-T, NM_001184917.2) in exon 11, resulting in a his244-to-tyr (H244Y) substitution, and a c.730C-T transition in exon 8, resulting in a pro307-to-leu (P307L; 602679.0002) substitution. Both mutations occurred at highly conserved residues in the CTP catalytic domain 2. The mutations, which were found by trio-based exome sequencing and confirmed by Sanger sequencing, were each inherited from the unaffected carrier parents. The H244Y variant was found at a low frequency (1.6 x 10(-5)) in heterozygous state in the gnomAD database, whereas P307L was not found in population databases. Analysis of mRNA in patient fibroblasts showed normal expression of the mutant transcripts, but Western blot analysis showed absence of the 49-kD protein that was observed in controls and decreased levels of the normal 42-kD protein seen in controls. Patient fibroblasts showed decreased, but not absent, PCYT2 enzymatic activity.


.0002 SPASTIC PARAPLEGIA 82, AUTOSOMAL RECESSIVE

PCYT2, PRO307LEU
  
RCV001003407

For discussion of the c.730C-T transition (c.730C-T, NM_001184917.2) in exon 8 of the PCYT2 gene, resulting in a pro307-to-leu (P307L) substitution, that was found in compound heterozygous state in a patient with autosomal recessive spastic paraplegia-82 (SPG82; 618770) by Vaz et al. (2019), see 602679.0001.


.0003 SPASTIC PARAPLEGIA 82, AUTOSOMAL RECESSIVE

PCYT2, ARG377TER
  
RCV001003408...

In 4 patients (patients 2 through 5) from 3 unrelated consanguineous families with autosomal recessive spastic paraplegia-82 (SPG82; 618770), Vaz et al. (2019) identified a homozygous c.1129C-T transition (c.1129C-T, NM_001184917.2) in the last exon (exon 14) of the PCYT2 gene, resulting in an arg377-to-ter (R377X) substitution. The mutation, which was found by exome sequencing and confirmed by Sanger sequencing through different laboratories, segregated with the disorder in all families. It was found at a low frequency (1.2 x 10(-4)) in heterozygous state in the gnomAD database. The mutation occurred in the last exon of 8 of 12 known PCYT2 transcripts, and was predicted to cause truncation of both the alpha and beta catalytically active isoforms. Analysis of mRNA in patient fibroblasts showed that the mutation escaped nonsense-mediated mRNA decay. Patient fibroblasts showed decreased, but not absent, PCYT2 enzymatic activities. Western blot analysis showed absence of the 49-kD protein that was observed in controls, decreased levels of the normal 42-kD protein seen in controls, as well as weak presence of an abnormal 46-kD protein.


.0004 SPASTIC PARAPLEGIA 82, AUTOSOMAL RECESSIVE

PCYT2, IVS12, G-A, +1
   RCV003881730

In a patient (case 1) with autosomal recessive spastic paraplegia-82 (SPG82; 618770), Kaiyrzhanov et al. (2021) identified compound heterozygous mutations in the PCYT2 gene: a c.1112+1G-A transition (c.1112+1G-A, NM_001184917.2), resulting in a splicing abnormality, and a c.743T-A transversion, resulting in a val230-to-glu (V230E; 602679.0004) substitution. The mutations were identified by whole-exome sequencing and confirmed by Sanger sequencing. Each parent carried one of the mutations. Analysis of cDNA from the patient demonstrated that the splicing mutation resulted in retention of intron 12 and a premature stop codon after 17 residues. The c.1112+1G-A mutation was not present in the gnomAD database, and the V230E mutation was present in 1 of 251,240 alleles in gnomAD.


.0005 SPASTIC PARAPLEGIA 82, AUTOSOMAL RECESSIVE

PCYT2, VAL230GLU
   RCV003881731

For a discussion of the c.743T-A transversion (c.743T-A, NM_001184917.2) in the PCYT2 gene, resulting in a val230-to-glu (V230E) substitution, that was identified in compound heterozygous state in a patient with autosomal recessive spastic paraplegia-82 (SPG82; 618770) by Kaiyrzhanov et al. (2021), see 602679.0004.


REFERENCES

  1. Christen, M., Oevermann, A., Rupp, S., Vaz, F. M., Wever, E. J. M., Braus, B. K., Jagannathan, V., Kehl, A., Hytonen, M. K., Lohi, H., Leeb, T. PCYT2 deficiency in Saarlooswolfdogs with progressive retinal, central, and peripheral neurodegeneration. Molec. Genet. Metab. 141: 108149, 2024. [PubMed: 38277988, related citations] [Full Text]

  2. Fullerton, M. D., Hakimuddin, F., Bakovic, M. Developmental and metabolic effects of disruption of the mouse CTP:phosphoethanolamine cytidylyltransferase gene (Pcyt2). Molec. Cell Biol. 27: 3327-3336, 2007. [PubMed: 17325045, images, related citations] [Full Text]

  3. Kaiyrzhanov, R., Wortmann, S., Reid, T., Dehghani, M., Vahidi Mehrjardi, M. Y., Alhaddad, B., Wagner, M., Deschauer, M., Cordts, I., Fernandez-Murray, J. P., Treffer, V., Metanat, Z., Pittman, A., Houlden, H., Meitinger, T., Carroll, C., McMaster, C. R., Maroofian, R. Defective phosphatidylethanolamine biosynthesis leads to a broad ataxia-spasticity spectrum. Brain 144: e30, 2021. Note: Erratum: Brain 144: e52, 2021. [PubMed: 33454747, related citations] [Full Text]

  4. Nakashima, A., Hosaka, K., Nikawa, J. Cloning of a human cDNA for CTP-phosphoethanolamine cytidylyltransferase by complementation in vivo of a yeast mutant. J. Biol. Chem. 272: 9567-9572, 1997. [PubMed: 9083101, related citations] [Full Text]

  5. Stumpf, A. M. Personal Communication. Baltimore, Md. 02/17/2020.

  6. Vaz, F. M., McDermott, J. H., Alders, M., Wortmann, S. B., Kolker, S., Pras-Raves, M. L., Vervaart, M. A. T., van Lenthe, H., Luyf, A. C. M., Elfrink, H. L., Metcalfe, K., Cuvertino, S., and 13 others. Mutations in PCYT2 disrupt etherlipid biosynthesis and cause a complex hereditary spastic paraplegia. Brain 142: 3382-3397, 2019. [PubMed: 31637422, images, related citations] [Full Text]


Hilary J. Vernon - updated : 02/23/2024
Hilary J. Vernon - updated : 08/18/2023
Anne M. Stumpf - updated : 02/17/2020
Cassandra L. Kniffin - updated : 02/06/2020
Creation Date:
Rebekah S. Rasooly : 6/2/1998
carol : 02/23/2024
carol : 08/18/2023
alopez : 02/17/2020
alopez : 02/17/2020
carol : 02/17/2020
carol : 02/14/2020
ckniffin : 02/06/2020
carol : 06/08/2012
psherman : 6/10/1998
psherman : 6/9/1998
psherman : 6/2/1998

* 602679

PHOSPHATE CYTIDYLYLTRANSFERASE 2, ETHANOLAMINE; PCYT2


Alternative titles; symbols

CYTIDYLYLTRANSFERASE, CTP-PHOSPHOETHANOLAMINE; ET
ETHANOLAMINE-PHOSPHATE CYTIDYLYLTRANSFERASE


HGNC Approved Gene Symbol: PCYT2

Cytogenetic location: 17q25.3     Genomic coordinates (GRCh38): 17:81,900,958-81,911,399 (from NCBI)


Gene-Phenotype Relationships

Location Phenotype Phenotype
MIM number
Inheritance Phenotype
mapping key
17q25.3 Spastic paraplegia 82, autosomal recessive 618770 Autosomal recessive 3

TEXT

Description

Phosphatidylethanolamine (PtdEtn; PE) is a major membrane phospholipid in both prokaryotic and eukaryotic cells. In the PtdEtn biosynthetic pathway, the enzyme CTP-phosphoethanolamine cytidylyltransferase (ET; EC 2.7.7.14) catalyzes the formation of CDP-ethanolamine from ethanolamine (summary by Nakashima et al., 1997). PE is one of the most abundant membrane lipids and is particularly enriched in the brain, where it represents about 45% of the phospholipid fraction (summary by Vaz et al., 2019).


Cloning and Expression

Nakashima et al. (1997) found that the S. cerevisiae ECT1 gene encodes ET. By screening a human glioblastoma cDNA expression library for the ability to complement a yeast ect1 mutation, they identified a cDNA encoding ET, or PCYT2. Expression of PCYT2 in yeast ect1 mutants restored ET activity. The sequence of the predicted 389-amino acid PCYT2 protein is 36% identical to that of the yeast ECT1 gene product. Northern blot analysis revealed that PCYT2 is expressed as an approximately 2-kb mRNA in various tissues, with strongest expression in liver, heart, and skeletal muscle.

Vaz et al. (2019) noted that the PCYT2 gene encodes at least 12 transcripts. The most abundant protein, cited in the article as a 44-kD isoform in some places and as a 42-kD isoform in others, which could represent the catalytically active isoform b. There is also a 49-kD isoform, which likely represents the catalytically active isoform a.


Gene Structure

Vaz et al. (2019) stated that the PCYT2 gene contains 14 exons.


Mapping

Stumpf (2020) mapped the PCYT2 gene to chromosome 17q25.3 based on an alignment of the PCYT2 sequence (GenBank AY251539.1) with the genomic sequence (GRCh38).


Molecular Genetics

In 5 patients from 4 unrelated families with autosomal recessive spastic paraplegia-82 (SPG82; 618770), Vaz et al. (2019) identified homozygous or compound heterozygous mutations in the PCYT2 gene (602679.0001-602679.0003). The mutations, which were found by exome sequencing and confirmed by Sanger sequencing through different laboratories, segregated with the disorder in all families. Patient fibroblasts showed significantly decreased, but not absent, PCYT2 activity compared to controls; residual activity ranged from 15 to 20% of controls. Western blot analysis showed absence of the normal 49-kD protein, with variably decreased levels of the normally most abundant isoform. Detailed lipidomic studies of patient fibroblasts showed several abnormalities, including accumulation of phosphatidylcholine etherphospholipids (PC(O)), neutral lipid species, and neutral etherlipid species. There was also a decrease in PE(O) (PE etherphospholipids) and PE/PC plasmalogen species. Patient blood samples also showed an abnormal accumulation of PC(O) compared to controls. Since some of the lipid levels did not reach expected levels of change, the authors suggested compensatory biochemical pathways. In summary, Vaz et al. (2019) concluded that etherlipid homeostasis is critical for the development and function of the brain.

In a patient (case 1) with SPG82, Kaiyrzhanov et al. (2021) identified compound heterozygous mutations in the PCYT2 gene (602679.0004 and 602679.0005). The mutations were identified by whole-exome sequencing and confirmed by Sanger sequencing. Each parent was heterozygous for one of the mutations.


Animal Model

Fullerton et al. (2007) found that Pcyt2-null mouse embryos died after implantation, prior to embryonic day 8.5.

Vaz et al. (2019) found that knockdown of the pcyt2 ortholog in zebrafish resulted in significantly decreased survival, poor growth, and abnormal tail-fin morphology.

Christen et al. (2024) identified a c.4A-G transition (XM_038546296.1) in the PCYT2 gene, predicted to result in an ile2-to-val substitution, in 11 Saarlooswolfdogs with progressive retinal and neurologic degeneration. The mutation was identified by linkage analysis, whole-genome sequencing, and Sanger sequencing. Phenotypic features included progressive retinal atrophy in 9 dogs and owner-reported blindness in 2 dogs. All 11 dogs had gait abnormalities, hindlimb weakness, tremors, ataxia, and cognitive changes. Histopathologic examination in a deceased 63-month-old affected dog demonstrated brain and spinal cord white matter astrocyte abnormalities, gliosis, and dilation of myelin sheaths. Lipidomic analysis in plasma from affected dogs demonstrated a significant accumulation of lipid ethers. Analysis of the mutation in a cohort of 998 healthy Saarlooswolfdogs demonstrated a mutant allele frequency of 9.9%.


ALLELIC VARIANTS 5 Selected Examples):

.0001   SPASTIC PARAPLEGIA 82, AUTOSOMAL RECESSIVE

PCYT2, HIS244TYR
SNP: rs1204173741, gnomAD: rs1204173741, ClinVar: RCV001003406, RCV001235496

In a 5.5-year-old boy (patient 1), born of unrelated Hungarian parents, with autosomal recessive spastic paraplegia-82 (SPG82; 618770), Vaz et al. (2019) identified compound heterozygous missense mutations in the PCYT2 gene: a c.920C-T transition (c.920C-T, NM_001184917.2) in exon 11, resulting in a his244-to-tyr (H244Y) substitution, and a c.730C-T transition in exon 8, resulting in a pro307-to-leu (P307L; 602679.0002) substitution. Both mutations occurred at highly conserved residues in the CTP catalytic domain 2. The mutations, which were found by trio-based exome sequencing and confirmed by Sanger sequencing, were each inherited from the unaffected carrier parents. The H244Y variant was found at a low frequency (1.6 x 10(-5)) in heterozygous state in the gnomAD database, whereas P307L was not found in population databases. Analysis of mRNA in patient fibroblasts showed normal expression of the mutant transcripts, but Western blot analysis showed absence of the 49-kD protein that was observed in controls and decreased levels of the normal 42-kD protein seen in controls. Patient fibroblasts showed decreased, but not absent, PCYT2 enzymatic activity.


.0002   SPASTIC PARAPLEGIA 82, AUTOSOMAL RECESSIVE

PCYT2, PRO307LEU
SNP: rs778113360, gnomAD: rs778113360, ClinVar: RCV001003407

For discussion of the c.730C-T transition (c.730C-T, NM_001184917.2) in exon 8 of the PCYT2 gene, resulting in a pro307-to-leu (P307L) substitution, that was found in compound heterozygous state in a patient with autosomal recessive spastic paraplegia-82 (SPG82; 618770) by Vaz et al. (2019), see 602679.0001.


.0003   SPASTIC PARAPLEGIA 82, AUTOSOMAL RECESSIVE

PCYT2, ARG377TER
SNP: rs377278120, gnomAD: rs377278120, ClinVar: RCV001003408, RCV002549210

In 4 patients (patients 2 through 5) from 3 unrelated consanguineous families with autosomal recessive spastic paraplegia-82 (SPG82; 618770), Vaz et al. (2019) identified a homozygous c.1129C-T transition (c.1129C-T, NM_001184917.2) in the last exon (exon 14) of the PCYT2 gene, resulting in an arg377-to-ter (R377X) substitution. The mutation, which was found by exome sequencing and confirmed by Sanger sequencing through different laboratories, segregated with the disorder in all families. It was found at a low frequency (1.2 x 10(-4)) in heterozygous state in the gnomAD database. The mutation occurred in the last exon of 8 of 12 known PCYT2 transcripts, and was predicted to cause truncation of both the alpha and beta catalytically active isoforms. Analysis of mRNA in patient fibroblasts showed that the mutation escaped nonsense-mediated mRNA decay. Patient fibroblasts showed decreased, but not absent, PCYT2 enzymatic activities. Western blot analysis showed absence of the 49-kD protein that was observed in controls, decreased levels of the normal 42-kD protein seen in controls, as well as weak presence of an abnormal 46-kD protein.


.0004   SPASTIC PARAPLEGIA 82, AUTOSOMAL RECESSIVE

PCYT2, IVS12, G-A, +1
ClinVar: RCV003881730

In a patient (case 1) with autosomal recessive spastic paraplegia-82 (SPG82; 618770), Kaiyrzhanov et al. (2021) identified compound heterozygous mutations in the PCYT2 gene: a c.1112+1G-A transition (c.1112+1G-A, NM_001184917.2), resulting in a splicing abnormality, and a c.743T-A transversion, resulting in a val230-to-glu (V230E; 602679.0004) substitution. The mutations were identified by whole-exome sequencing and confirmed by Sanger sequencing. Each parent carried one of the mutations. Analysis of cDNA from the patient demonstrated that the splicing mutation resulted in retention of intron 12 and a premature stop codon after 17 residues. The c.1112+1G-A mutation was not present in the gnomAD database, and the V230E mutation was present in 1 of 251,240 alleles in gnomAD.


.0005   SPASTIC PARAPLEGIA 82, AUTOSOMAL RECESSIVE

PCYT2, VAL230GLU
ClinVar: RCV003881731

For a discussion of the c.743T-A transversion (c.743T-A, NM_001184917.2) in the PCYT2 gene, resulting in a val230-to-glu (V230E) substitution, that was identified in compound heterozygous state in a patient with autosomal recessive spastic paraplegia-82 (SPG82; 618770) by Kaiyrzhanov et al. (2021), see 602679.0004.


REFERENCES

  1. Christen, M., Oevermann, A., Rupp, S., Vaz, F. M., Wever, E. J. M., Braus, B. K., Jagannathan, V., Kehl, A., Hytonen, M. K., Lohi, H., Leeb, T. PCYT2 deficiency in Saarlooswolfdogs with progressive retinal, central, and peripheral neurodegeneration. Molec. Genet. Metab. 141: 108149, 2024. [PubMed: 38277988] [Full Text: https://doi.org/10.1016/j.ymgme.2024.108149]

  2. Fullerton, M. D., Hakimuddin, F., Bakovic, M. Developmental and metabolic effects of disruption of the mouse CTP:phosphoethanolamine cytidylyltransferase gene (Pcyt2). Molec. Cell Biol. 27: 3327-3336, 2007. [PubMed: 17325045] [Full Text: https://doi.org/10.1128/MCB.01527-06]

  3. Kaiyrzhanov, R., Wortmann, S., Reid, T., Dehghani, M., Vahidi Mehrjardi, M. Y., Alhaddad, B., Wagner, M., Deschauer, M., Cordts, I., Fernandez-Murray, J. P., Treffer, V., Metanat, Z., Pittman, A., Houlden, H., Meitinger, T., Carroll, C., McMaster, C. R., Maroofian, R. Defective phosphatidylethanolamine biosynthesis leads to a broad ataxia-spasticity spectrum. Brain 144: e30, 2021. Note: Erratum: Brain 144: e52, 2021. [PubMed: 33454747] [Full Text: https://doi.org/10.1093/brain/awaa442]

  4. Nakashima, A., Hosaka, K., Nikawa, J. Cloning of a human cDNA for CTP-phosphoethanolamine cytidylyltransferase by complementation in vivo of a yeast mutant. J. Biol. Chem. 272: 9567-9572, 1997. [PubMed: 9083101] [Full Text: https://doi.org/10.1074/jbc.272.14.9567]

  5. Stumpf, A. M. Personal Communication. Baltimore, Md. 02/17/2020.

  6. Vaz, F. M., McDermott, J. H., Alders, M., Wortmann, S. B., Kolker, S., Pras-Raves, M. L., Vervaart, M. A. T., van Lenthe, H., Luyf, A. C. M., Elfrink, H. L., Metcalfe, K., Cuvertino, S., and 13 others. Mutations in PCYT2 disrupt etherlipid biosynthesis and cause a complex hereditary spastic paraplegia. Brain 142: 3382-3397, 2019. [PubMed: 31637422] [Full Text: https://doi.org/10.1093/brain/awz291]


Contributors:
Hilary J. Vernon - updated : 02/23/2024
Hilary J. Vernon - updated : 08/18/2023
Anne M. Stumpf - updated : 02/17/2020
Cassandra L. Kniffin - updated : 02/06/2020

Creation Date:
Rebekah S. Rasooly : 6/2/1998

Edit History:
carol : 02/23/2024
carol : 08/18/2023
alopez : 02/17/2020
alopez : 02/17/2020
carol : 02/17/2020
carol : 02/14/2020
ckniffin : 02/06/2020
carol : 06/08/2012
psherman : 6/10/1998
psherman : 6/9/1998
psherman : 6/2/1998