- Aug 2024
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drive.google.com drive.google.com
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Case: Patient #32, Female
DiseaseAssertion: UCD/OTCD
FamilyInfo: N/A
CasePresentingHPOs: N/A
CaseHPOFreeText:
CaseNOTHPOs:
CaseNOTHPOFreeText:
CasePreviousTesting: N/A
Variant: NM_000531.6: c.140dup (p.(Asn47LysfsTer8))
ClinVarID:
CAID:
gnomAD:
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Case: Patient #7, Female
DiseaseAssertion: UCD/OTCD
FamilyInfo: N/A
CasePresentingHPOs: N/A
CaseHPOFreeText:
CaseNOTHPOs:
CaseNOTHPOFreeText:
CasePreviousTesting: N/A
Variant: NM_000531.6: c.29_32del (p.Asn10fs)
ClinVarID: 97157
CAID: CA224540
gnomAD:
Gene Name: OTC (ornithine transcarbamylase)
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- Jul 2024
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drive.google.com drive.google.com
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Case: 24 yo Laotse patient , female
Disease Assertion: UCD/OTCD
Family Info:
Case Presenting HPOs:Hyperammonemia(HP:0001987), Adult onset (HP:0003581), Elevated circulating alanine aminotransferase concentration(HP:0031964), Elevated circulating aspartate aminotransferase concentration(HP:0031956), oriticaciduria(HP:0003218), Aminoaciduria(HP:0003355, Prolonged prothrombin time(HP:0008151), Cerebral edema(HP:0002181),
Case HPO FreeText:
Case NOT HPOs:
Case NOT HPO Free Text:
Case Previous Testing: " Genomic DNA from the patient was isolated from cultivated fibroblasts. Nine pairs of primers were designed from the published sequence of the OTC gene6,7 to allow amplification of all 10 exons including adjacent intron sequences. Single-strand conformational polymorphism analysis of the polymerase chain reaction–amplified individual exon 8 yielded an unusual migration pattern of exon 9
Supplemental Data: Case report section Notes: Patient had a pregnancy 2 years prior and lost the baby. In this case report, She was a 14weeks pregnant(2nd pregnancy) 24yo . She died during this of severe hyperammonemia 5 days after being administered amino acids through parenteral nutrition. She developed signs of encephalopathy stage 4 with maximal dilated unresponsive pupils, brisk oculocephalic reflex, and severe hyperventilation, requiring mechanical ventilation. MRI revealed revealed diffuse cortical edema with loss of white to gray matter distinction. Increased excretion of Gly, Gln, Ser, Thr, and Lys was found in her urine. Treatment with benzoate was started but didn't save the patient.
Variant: NM_000531.6: c.892_893del(p.Trp298Aspfs*15)
ClinVarID: 97348
CAID: CA224820
gnomAD:
Gene Name: OTC (ornithine transcarbamylase)
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drive.google.com drive.google.com
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Case: patient #20, Male
Disease Assertion: UCD/OTCD
Family Info: NA
Case Presenting HPOs: Hyperammonemia (HP:0001987), oriticaciduria (HP:0003218), low plasma citrulline (HP:0003572), neonatal onset (HP:0003623)
Case HPO FreeText:
Case NOT HPOs:
Case NOT HPO Free Text:
Case Previous Testing: Genomic DNA was isolated using PUREGENE blood kit from peripheral leukocytes of patients and related family members with informed consents. Amplification by PCR of all 10 exons of the OTC gene was performed using nine pairs of primers designed to span all exons and their adjacent intronic regions. PCR products were subsequently sequenced using ABI3100 Genetic analyzer with BigDye termination ver.3.0.To analyze the activity of OTC protein expressed in the COS-7, high-pressure liquid chromatographic (HPLC) analysis was performed with a Water system, consisting of a model 510 pump and a UV-visible 420 detector.
Supplemental Data: Table 1 Notes:
Variant: NM_000531.6: c.796_805del(p.Ile265AspfsX20)
ClinVarID: NA
CAID: CA2695233326
gnomAD:
Gene Name: OTC (ornithine transcarbamylase)
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drive.google.com drive.google.com
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Case: patient #1, female Disease Assertion: UCD/OTCD
Family Info:
Case Presenting HPOs: Hyperammonemia (HP:0001987), Juvenile onset (HP:0003621)
Case HPO FreeText:
Case NOT HPOs:
Case NOT HPO Free Text:
Case Previous Testing: "DNA samples were obtained from either peripheral white blood cells or liver biopsies of probands. Patient 1 total liver RNAs were extracted by the acid-phenol-guanidium method and reverse-transcribed in cDNA by hexanucleotide priming using Superscript 11' (Life Technologies, Cergy-Pantoia, France). First strand cDNA was further PCR-amplified using forward and reverse primers specificons 7 and 9 of the OTC gene, respectively. Sequence comparisons were conducted using the FASTA option of the BISANCE package. Secondary protein conformational changes induced by sequence mutations were predicted using the algorithms of the BISANCE package. Nucleotidic changes potentially altering splice sites were studied using the Senapathy's algorithm from the BISANCE package."
Supplemental Data: TABLE 1, Notes:
Variant: NM_000531.6: c.731_739del(p.Leu244Profs)
ClinVarID: 97307
CAID: CA224765
gnomAD:
Gene Name: OTC (ornithine transcarbamylase)
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drive.google.com drive.google.com
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Case: patient #273, Male
Disease Assertion: UCD/OTCD
Family Info: NA
Case Presenting HPOs: Neonatal onset (HP:0003623)
Case HPO FreeText:
Case NOT HPOs:
Case NOT HPO Free Text:
Case Previous Testing: NA
Supplemental Data: Supplemental table file Notes:
Variant: NM_000531.6: c.818del (p.Glu273Glyfs*16)
ClinVarID: 97338
CAID: CA224807
gnomAD:
Gene Name: OTC (ornithine transcarbamylase)
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drive.google.com drive.google.com
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Case: no patient #ID, female Disease Assertion: UCD/OTCD
Family Info: NA
Case Presenting HPOs: NA
Case HPO FreeText:
Case NOT HPOs:
Case NOT HPO Free Text:
Case Previous Testing: NA
Supplemental Data: TABLE 1, Notes: NA
Variant: NM_000531.6: c.665del(p.(Gly222ValfsTer8)
ClinVarID: 97289
CAID: CA224738
gnomAD:
Gene Name: OTC (ornithine transcarbamylase)
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drive.google.com drive.google.com
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Case: patient #5, female
Disease Assertion: UCD/OTCD
Family Info: N/A
Case Presenting HPOs: Neonatal onset (HP:0003623)
Case HPO FreeText:
Case NOT HPOs:
Case NOT HPO Free Text:
Case Previous Testing: gDNA testing involves PCR amplification of all 10 exons and exon/intron boundaries followed by screening for mutations or sequencing of all fragments, For these patients, confirmation of the diagnosis requires enzymatic assays. No specifications about the test
Supplemental Data: TABLE 1
Variant: NM_000531.6: c.53del (p.His18Profs*20)
ClinVarID: 97239
CAID: CA224671
gnomAD:
Gene Name: OTC (ornithine transcarbamylase)
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Case: patient #85, female
Disease Assertion: UCD/OTCD
Family Info: N/A
Case Presenting HPOs:
Case HPO FreeText:
Case NOT HPOs:
Case NOT HPO Free Text:
Case Previous Testing: gDNA testing involves PCR amplification of all 10 exons and exon/intron boundaries followed by screening for mutations or sequencing of all fragments, For these patients, confirmation of the diagnosis requires enzymatic assays. No specifications about the test
Supplemental Data: TABLE 1
Variant: NM_000531.6: c.449_451del(p.Leu151Trpfs*36)
ClinVarID: N/A
CAID: CA2759533410
gnomAD:
Gene Name: OTC (ornithine transcarbamylase)
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Case: patient #154, male
Disease Assertion: UCD/OTCD
Family Info: N/A
Case Presenting HPOs: Neonatal onset (HP:0003623)
Case HPO FreeText:
Case NOT HPOs:
Case NOT HPO Free Text:
Case Previous Testing: gDNA testing involves PCR amplification of all 10 exons and exon/intron boundaries followed by screening for mutations or sequencing of all fragments, For these patients, confirmation of the diagnosis requires enzymatic assays. No specifications about the test
Supplemental Data: TABLE 1
Variant: NM_000531.6: c.664-1G>A
ClinVarID: 97288
CAID: CA224811
gnomAD:
Gene Name: OTC (ornithine transcarbamylase)
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drive.google.com drive.google.com
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Case: patient #335, female
Disease Assertion: UCD/OTCD
Family Info: N/A
Case Presenting HPOs:
Case HPO FreeText:
Case NOT HPOs:
Case NOT HPO Free Text:
Case Previous Testing: No specific functional tests indicated
Supplemental Data: In supplemental data files
Variant: NM_000531.6: c.861_862insAC (p.Met288Thrfs*2)
ClinVarID: N/A
CAID: CA2759522140
gnomAD:
Gene Name: OTC (ornithine transcarbamylase)
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Case: patient #212, female
Disease Assertion: UCD/OTCD
Family Info: N/A
Case Presenting HPOs:
Case HPO FreeText:
Case NOT HPOs:
Case NOT HPO Free Text:
Case Previous Testing: No specific functional tests indicated
Supplemental Data: In supplemental data files
Variant: NM_000531.6:c.561delA(p.Gly188Valfs*18)
ClinVarID: N/A
CAID: CA2499307429
gnomAD:
Gene Name: OTC (ornithine transcarbamylase)
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drive.google.com drive.google.com
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Case: patient #55, male, Japanese
Disease Assertion: UCD/OTCD
Family Info: N/A
Case Presenting HPOs: Seizure (HP:0001250), Hyperammonemia (HP:0001987), Intellectual disability (HP:0001249)
Case HPO FreeText: abnormal brain MRI and brain waves, acute liver failure, corneal opacity
Case NOT HPOs:
Case NOT HPO Free Text:
Case Previous Testing: The mRNA ref seq were, wherein the “A” nucleotide of the start codon ATG constituted as +1 numbering of the cDNA sequence. Met encoded by the start codon ATG also represented +1 for the amino acid numbering as set forth by the preprotein seq. PolyPhen-2, SIFT, and I-Mutant 3 tools were used for predicting the potential impact of an amino acid alteration in missense mutations on the function of each enzyme.
Supplemental Data: Table 1
Variant: NM_000531.6:c.c.929_931del(p.Glu310Valfs*45)
ClinVarID: 858012
CAID: CA916083888
gnomAD:
Gene Name: OTC (ornithine transcarbamylase)
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Case: patient #50, male, Japanese
Disease Assertion: UCD/OTCD
Family Info: N/A
Case Presenting HPOs: Seizure HP:0001250, hyperammonemia HP: 0001987
Case HPO FreeText: Hepatomegaly, Abnormal brain MRI and brain waves, Acute liver failure, Corneal opacity
Case NOT HPOs:
Case NOT HPO Free Text:
Case Previous Testing: The mRNA ref seq were, wherein the “A” nucleotide of the start codon ATG constituted as +1 numbering of the cDNA sequence. Met encoded by the start codon ATG also represented +1 for the amino acid numbering as set forth by the preprotein seq. PolyPhen-2, SIFT, and I-Mutant 3 tools were used for predicting the potential impact of an amino acid alteration in missense mutations on the function of each enzyme.
Supplemental Data: Table 1
Variant: NM_000531.6:c.834_840del(p.Gln279Serfs*8)
ClinVarID: N/A
CAID: CA2695233329
gnomAD:
Gene Name: OTC (ornithine transcarbamylase)
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drive.google.com drive.google.com
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Case: no patient ID, Female
Disease Assertion: UCD/OTCD
Family Info: N/A
Case Presenting HPOs: HP:0001951, HP: 0001987
Case HPO FreeText: episodic hyperammonemia, hyperammonemia
Case NOT HPOs:
Case NOT HPO Free Text:
Case Previous Testing: "Genomic DNAs were extracted from leukocytes, The ten exons and intron-exon boundaries of the OTC gene were PCR amplified and analyzed by Sanger sequencing on an ABI3100 sequencer. Intragenic deletions/duplications were searched for by Multiple Ligation Probe Dependent Amplification assay. Potential impact of non truncating variants on mRNA and protein was predicted using Splice Site Prediction. OTC variants were split into two groups, “severe” and “mild,” based on their impact on the clinical phenotype and on the OTC protein.
Supplemental Data: Table 3, All nuclear family members were tested but no information about their genotype. the condition to be part of this study was the presence of at least one heterozygous female in the pedigree of the patient.
Variant: NM_000531.6:c.1052delA(p.Lys351Serfs*44)
ClinVarID: 915468
CAID: CA1139667400
gnomAD:
Gene Name: OTC (ornithine transcarbamylase)
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Case: no patient ID, Female
Disease Assertion: UCD/OTCD
Family Info: N/A
Case Presenting HPOs: HP:0001951, HP: 0001987
Case HPO FreeText: episodic hyperammonemia, hyperammonemia
Case NOT HPOs:
Case NOT HPO Free Text:
Case Previous Testing: "Genomic DNAs were extracted from leukocytes, The ten exons and intron-exon boundaries of the OTC gene were PCR amplified and analyzed by Sanger sequencing on an ABI3100 sequencer. Intragenic deletions/duplications were searched for by Multiple Ligation Probe Dependent Amplification assay. Potential impact of non truncating variants on mRNA and protein was predicted using Splice Site Prediction. OTC variants were split into two groups, “severe” and “mild,” based on their impact on the clinical phenotype and on the OTC protein.
Supplemental Data: Table 3, All nuclear family members were tested but no information about their genotype. the condition to be part of this study was the presence of at least one heterozygous female in the pedigree of the patient.
Variant: NM_000531.6:c.568dupA(p.Thr190Asnfs*35)
ClinVarID: 870328
CAID: CA916083887
gnomAD:
Gene Name: OTC (ornithine transcarbamylase)
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drive.google.com drive.google.com
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Case: Patient #27, male, Korean
Disease Assertion: UCD/OTCD
Family Info: N/A
Case Presenting HPOs: HP:0003593, HP:0003218, HP: 0001987
Case HPO FreeText: Infantile onset, oroticaciduria, hyperammonemia
Case NOT HPOs:
Case NOT HPO Free Text:
Case Previous Testing: "Potential impact of mutations on OTC function and/or folding assessed by multiple alignments of orthologous protein sequences and human OTC and structural data from Protein Data Bank (1C9Y and available orthologs). In M patients, the approximate extent of the deletions assessed by inspection of presence/absence of PCR products. In F patients, the deletions determined by the SALSA multiplex ligation probe amplification (MLPA) KIT P079 OTC (MRC-Holland, Amsterdam, the Netherlands) and the Affymetrix Human SNP 6.0 array (Santa Clara, CA). Sequence spanning 38,211,736 – 38,300,703 bp region on chromosome X (GRCh37) and including OTC was scanned for motifs CCTCCCT, CCTCCTT, CCTCCCTT, CCCCACCCC, CCNCCNTNNCCNC, GGNGGNAGGG and their complements known as being associated with recombination hotspots. Repeats capable of non-B DNA structure formation implicated in double strand breaks (DSBs) were sought by complexity analysis . X-inactivation ratio determined by analysis of methylation status of the human androgen-receptor locus (HUMARA)
Supplemental Data: Table 1&2, The minimum plasma ammonia, orotic acid and Gln+Glu concentrations depends on certain age range: Plasma ammonia: neonates <90μmol/l, other <60μmol/l. Urinary orotic acid: 0–1year <6.6mmol/mol creatinine, 1 – 10 years <3.5 mmol/mol creatinine, over 10 years <2.4 mmol/mol creatinine. Serum glutamate + glutamine: 0 – 1 month 200–1200μmol/l, 1 month–1year 200–1100μmol/l, 1year–18years 200–900μmol/l, over 18years 200–800μmol/l.
Variant: NM_000531.6:c.929_931del(p.Glu310Valfs*45)
ClinVarID: N/A
CAID: CA916083888
gnomAD:
Gene Name: OTC (ornithine transcarbamylase)
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Case: Patient #37, female, Korean
Disease Assertion: UCD/OTCD
Family Info: N/A
Case Presenting HPOs: HP:0011463, HP:0003218, HP: 0001987
Case HPO FreeText: Childhood onset, oroticaciduria, hyperammonemia
Case NOT HPOs:
Case NOT HPO Free Text:
Case Previous Testing: "Potential impact of mutations on OTC function and/or folding assessed by multiple alignments of orthologous protein sequences and human OTC and structural data from Protein Data Bank (1C9Y and available orthologs). In M patients, the approximate extent of the deletions assessed by inspection of presence/absence of PCR products. In F patients, the deletions determined by the SALSA multiplex ligation probe amplification (MLPA) KIT P079 OTC (MRC-Holland, Amsterdam, the Netherlands) and the Affymetrix Human SNP 6.0 array (Santa Clara, CA). Sequence spanning 38,211,736 – 38,300,703 bp region on chromosome X (GRCh37) and including OTC was scanned for motifs CCTCCCT, CCTCCTT, CCTCCCTT, CCCCACCCC, CCNCCNTNNCCNC, GGNGGNAGGG and their complements known as being associated with recombination hotspots. Repeats capable of non-B DNA structure formation implicated in double strand breaks (DSBs) were sought by complexity analysis . X-inactivation ratio determined by analysis of methylation status of the human androgen-receptor locus (HUMARA)
Supplemental Data: Table 1&2, The minimum plasma ammonia, orotic acid and Gln+Glu concentrations depends on certain age range: Plasma ammonia: neonates <90μmol/l, other <60μmol/l. Urinary orotic acid: 0–1year <6.6mmol/mol creatinine, 1 – 10 years <3.5 mmol/mol creatinine, over 10 years <2.4 mmol/mol creatinine. Serum glutamate + glutamine: 0 – 1 month 200–1200μmol/l, 1 month–1year 200–1100μmol/l, 1year–18years 200–900μmol/l, over 18years 200–800μmol/l.
Variant: NM_000531.6:c.1043delA(p.Gln348Argfs*47)
ClinVarID: N/A
CAID: CA2695233335
gnomAD:
Gene Name: OTC (ornithine transcarbamylase)
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Case: Patient #6, male, Korean
DiseaseAssertion: UCD/OTCD
FamilyInfo: N/A
CasePresentingHPOs: HP:0011463, HP:0001987, HP:0003218
CaseHPOFreeText: Neonatal onset, hyperammonemia, oroticaciduria,
CaseNOTHPOs:
CaseNOTHPOFreeText:
CasePreviousTesting: "Potential impact of mutations on OTC function and/or folding assessed by multiple alignments of orthologous protein sequences and human OTC and structural data from Protein Data Bank (1C9Y and available orthologs). In M patients, the approximate extent of the deletions assessed by inspection of presence/absence of PCR products. In F patients, the deletions determined by the SALSA multiplex ligation probe amplification (MLPA) KIT P079 OTC (MRC-Holland, Amsterdam, the Netherlands) and the Affymetrix Human SNP 6.0 array (Santa Clara, CA). Sequence spanning 38,211,736 – 38,300,703 bp region on chromosome X (GRCh37) and including OTC was scanned for motifs CCTCCCT, CCTCCTT, CCTCCCTT, CCCCACCCC, CCNCCNTNNCCNC, GGNGGNAGGG and their complements known as being associated with recombination hotspots. Repeats capable of non-B DNA structure formation implicated in double strand breaks (DSBs) were sought by complexity analysis . X-inactivation ratio determined by analysis of methylation status of the human androgen-receptor locus (HUMARA)
Supplemental Data: Table 1&2, the minimum plasma ammonia, orotic acid and Gln+Glu concentrations depends on certain age range: Plasma ammonia: neonates <90μmol/l, other <60μmol/l. Urinary orotic acid: 0–1year <6.6mmol/mol creatinine, 1 – 10 years <3.5 mmol/mol creatinine, over 10 years <2.4 mmol/mol creatinine. Serum glutamate + glutamine: 0 – 1 month 200–1200μmol/l, 1 month–1year 200–1100μmol/l, 1year–18years 200–900μmol/l, over 18years 200–800μmol/l.
Variant: NM_000531.6:c.461_471del(p.Glu154Alafs*18)
ClinVarID: N/A
CAID:CA2695233305
gnomAD:
GeneName: OTC (ornithine transcarbamylase)
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drive.google.com drive.google.com
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Case: Patient #15, male, Korean
DiseaseAssertion: UCD/OTCD
FamilyInfo: N/A
CasePresentingHPOs: HP:0011463, HP:0001987, HP:0003218, HP:0003572
CaseHPOFreeText: Neonatal onset, hyperammonemia, oroticaciduria, low plasma citrulline
CaseNOTHPOs:
CaseNOTHPOFreeText:
CasePreviousTesting: Genomic DNA was extracted from peripheral blood leukocytes. A total of 10 coding exons and exon–intron boundaries of the OTC gene were amplified by PCR with customized primers. PCR products were directly sequenced with the same primers . Sequencing results were compared with the established human OTC sequences(NM_000531.5). Multiplex ligation-dependent probe amplification analysis was performed for patients in whom no OTC mutations were identified by direct sequencing using the OTC MLPA kit.
Supplemental Data: Table 1, mother is a carrier, no range was given for blood ammonia concentration, range given in the tables for glutamine and urine orotate is slightly different than the one in the results paragraphs.
Variant: NM_000531.6:c.796_805del(p.Ile265_Gly268delinsAspfs*19)
ClinVarID: N/A
CAID:CA2695233326
gnomAD:
GeneName: OTC (ornithine transcarbamylase)
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Case: Patient #45, female, Korean
DiseaseAssertion: UCD/OTCD
FamilyInfo: variant in mother (father not tested) and brother
CasePresentingHPOs: HP:0003593, HP:0001987, HP:0003218
CaseHPOFreeText: infantile onset, hyperammonemia, oroticaciduria
CaseNOTHPOs:
CaseNOTHPOFreeText:
CasePreviousTesting: Genomic DNA was extracted from peripheral blood leukocytes. A total of 10 coding exons and exon–intron boundaries of the OTC gene were amplified by PCR with customized primers. PCR products were directly sequenced with the same primers . Sequencing results were compared with the established human OTC sequences(NM_000531.5). Multiplex ligation-dependent probe amplification analysis was performed for patients in whom no OTC mutations were identified by direct sequencing using the OTC MLPA kit.
Supplemental Data: Table 1, mother is a carrier, the mutation was also found in patient 13(her brother), no range was given for blood ammonia concentration, range given in the tables for glutamine and urine orotate is slightly different than the one in the results paragraphs.
Variant: NM_000531.6c.664_667delinsAC(p.Gly222Thrfs*2)
ClinVarID: N/A
CAID:CA2695233319
gnomAD:
GeneName: OTC (ornithine transcarbamylase)
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Case: Patient #44, female, Korean
DiseaseAssertion: UCD/OTCD
FamilyInfo: variant in mother (father not tested)
CasePresentingHPOs: HP:0011463, HP:0001987, HP:0003218, HP:0003217
CaseHPOFreeText: Childhood onset, hyperammonemia, oroticaciduria, hyperglutaminemia
CaseNOTHPOs:
CaseNOTHPOFreeText:
CasePreviousTesting: Genomic DNA was extracted from peripheral blood leukocytes. A total of 10 coding exons and exon–intron boundaries of the OTC gene were amplified by PCR with customized primers. PCR products were directly sequenced with the same primers . Sequencing results were compared with the established human OTC sequences(NM_000531.5). Multiplex ligation-dependent probe amplification analysis was performed for patients in whom no OTC mutations were identified by direct sequencing using the OTC MLPA kit.
Supplemental Data: Table 1, mother is a carrier, no range was given for blood ammonia concentration, range given in the tables for glutamine and urine orotate is slightly different than the one in the results paragraphs.
Variant: NM_000531.6:c.799_800insA (p.Ser267Lysfs*26)
ClinVarID: N/A
CAID:CA2695233327
gnomAD:
GeneName: OTC (ornithine transcarbamylase)
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drive.google.com drive.google.com
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Case: Patient #30, male, Chinese
DiseaseAssertion: UCD/OTCD
FamilyInfo: no family history of the disease
CasePresentingHPOs: HP:0003593, HP:0001987, HP:0003218
CaseHPOFreeText: infantile onset, hyperammonemia, oroticaciduria
CaseNOTHPOs:
CaseNOTHPOFreeText: No neurological damage
CasePreviousTesting: gDNA extracted from peripheral blood leukocytes. PCR all coding exons and exon–intron boundaries of the OTC gene using 9 pairs of synthetic oligonucleotide primers, and the primer sequences and annealing temperature. PCR products were then purified and bidirectionally sequenced. The library was sequenced using Illumina HiSeq4000 and generated 150 bp paired-end reads. Data analysis was performed as previously described [Sun Y, Hu G, Liu H, Zhang X, Huang Z, Yan H, et al. Further delineation of the phenotype of truncating KMT2A mutations: the extended Wiedemann–Steiner syndrome. Am J Med Genet A. 2017;173:510–4.]. Multiplex ligation-dependent probe amplification analysis was performed for samples in which Sanger sequencing or WES failed to detect any disease-causing mutation.
SupplementalData: Table 3, drug treatment(L-arginine, L-Citrulline, sodium benzoate, and sodium phenylbutyrate)
Variant: NM_000531.6:c.929_931del(p.Glu310Valfs*45)
ClinVarID: 858012
CAID:CA916083888
gnomAD:
GeneName: OTC (ornithine transcarbamylase)
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- Oct 2023
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tante.cc tante.cc
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A few years ago YouTube (of course others joined in and followed but I think YouTube was a leading force here) established the term “content”. It was no longer about the actual qualities of the medium, not about videos or music or stories or essays etc. Everything one made was just content.
FrameShift
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- May 2022
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www.ncbi.nlm.nih.gov www.ncbi.nlm.nih.gov
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DICER1 syndrome encompasses a variety of benign and malignant manifestations including multinodular goitre
Gene: DICER1 PMCID: PMC8451242 PMID: 34552563 Pathogenic Inheritance Pattern: Autosomal Dominant MultipleDiseaseEntities Disease Entity: DICER1 syndrome, multinodular goitre, cystic nephroma, anaplastic renal sarcoma, Wilms tumour, differentiated thyroid carcinoma, gynandroblastoma, ciliary body medulloepithelioma, embryonal rhabdomyosarcoma, pineoblastoma, pituitary blastoma, kidney cyst, pulmonary cyst, Sertoli-Leydig Cell Tumor. Mutation: Germline MultipleGeneVariants Variant & Clinvar IDs: c.3452_3453del (485534), c.316del (no ClinVar ID), c.171_172insAC (no ClinVar ID), c.3434del (no ClinVar ID), c.988C>T (933007), c.5388dup (no ClinVar ID) Zygosity: None provided. Case: At time of operation, the goitre patients living in Denmark were ages 21, 12, 21, 8, 14, and 16. Four underwent total thyroidectomies, and two underwent partial thyroidectomies. The patient originally aged 21 previously had a kidney cyst at age 14 and a pulmonary cyst at an unknown age. The patient aged 14 at time of partial thyroidectomy later manifested a Sertoli-Leydig Cell Tumor at age 15. All six patients were female. CasePresentingHPO: None provided. CasePreviousTesting: thyroidectomy gnomAD: ENSG00000100697.10, https://gnomad.broadinstitute.org/gene/ENSG00000100697 Mutation Type: Frameshift, Nonsense
Tags
- goitre
- ClinvarID:933007
- MultipleDiseaseEntities
- PMCID:PMC8451242
- Cohort
- ClinvarID:NotProvided
- DICER1
- c.316del
- PMID:34552563
- female
- thyroidectomy
- AutosomalDominant
- MultipleGeneVariants
- Nonsense
- Pathogenic
- Germline
- Age:12
- c.171_172insAC
- goiter
- c.3434del
- cancer
- Mutation:Nonsense
- ClinvarID:485534
- Age:21
- Mutation:Frameshift
- c.3452_3453del
- c.5388dup
- Age:8
- Frameshift
- gnomAD:ENSG00000100697.10
- c.988C>T
- Age:14
- Gene:DICER1
Annotators
URL
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www.ncbi.nlm.nih.gov www.ncbi.nlm.nih.gov
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DICER1 syndrome is a rare genetic condition predisposing to hereditary cancer and caused by variants in the DICER1
GeneName: DICER1 PMCID: PMC7859642 HGNCID: Unavailable Inheritance Pattern: Autosomal dominant. Disease Entity: Familial pleuropulmonary blastoma (PPB), cervix embryonal rhabdomyosarcoma, multinodular goiter, nasal chondromesenchymal hemartoma, Ciliary body medulloepithelioma, Sertoli-Leydig Cell Tumor (SLCT), differentiated thyroid carcinoma, pituitary blastoma, pineoblastoma, cystic nephroma, Wilm's tumor and sarcomas of different sites including, amongst others, the uterine cervix, kidney and brain. Mutation: Germline Zygosity: Heterozygose Variant: No ClinVarID present. Family Information: No family outline Case: No specified information of patients included. CasePresentingHPO's: n/a CasePrevious Testing: n/a gnomAD: n/a Mutation Type: nonsense, frameshift, or splice affected.
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DICER1 syndrome is a rare genetic condition predisposing to hereditary cancer and caused by variants in the DICER1 gene.
GeneName: DICER1 PMID: 33552988 HGNCID: Unavailable Inheritance Pattern: Autosomal Dominant with reduced penetrance Disease Entity: Cystic nephroma, familial pleuropulmonary blastoma (PPB), ovarian Sertoli-Leydig cell tumor (SLCT), cervix embryonal rhabdomyosarcoma, multinodular goiter, Wilms' Tumor, Ciliary body medulloepithelioma, nasal chondromesenchymal hamartoma, differentiated thyroid carcinoma, pituitary blastoma, pineoblastoma, sarcomas of different sites. Mutation: germline mutation Zygosity: heterozygous Variant: ClinVar ID not listed Family Information: No family cases listed Case: No specific case mentioned gnomAD: N/A Mutation Type: Frameshift, Nonsense mutation
Tags
- Cervix embryonal rhabdomyosarcoma
- Wilms'tumor
- Multinodular goiter
- Mutation type: Nonsense
- Inheritance Pattern: Autosomal dominant
- Cancer
- Wilm's tumor
- PPB
- PMCID: PMC7859642
- Mutation type: Frameshift
- Mutation: Germline
- Sertoli-Letdig Cell Tumor(SLCT)
- Frameshift
- Gene: DICER1
- Familial pleuropulmonary blastoma (PPB)
- PMID:33552988
- SLCT
- Sarcomas
- AutosomalDominant
- Nonsense
- Differentiated thyroid carcinoma
- Zygosity: Heterozygous
- Germline
- Nasal chondromesenchymal hemartoma
- Gene:DICER1
- Ciliary body medulloepitheliomma
Annotators
URL
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- Apr 2022
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www.ncbi.nlm.nih.gov www.ncbi.nlm.nih.gov
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DICER1 syndrome is a rare genetic condition predisposing to hereditary cancer and caused by variants in the DICER1 gene.
Gene Name: DICER1 PMID:33552988 HGNCID: Unavailable Inheritance Pattern:Autosomal Dominant Disease Entity: familial pleuropulmonary blastoma (PPB),cystic nephroma, ovarian Sertoli-Leydig cell tumor (SLCT), multinodular goiter, cervix embryonal rhabdomyosarcoma, Wilms’ tumor, nasal chondromesenchymal hamartoma, ciliary body medulloepithelioma, differentiated thyroid carcinoma, pituitary blastoma, pineoblastoma, and sarcomas of different sites. Mutation: Nonsense, Frameshift<br /> Zygosity: Heterosygosity Variant:No ClinVar ID present Family Information:no diseases mentioned in family Case: no specified case in this article gnomAD: n/a Mutation type: Nonsense. frameshift
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DICER1 syndrome is a cancer-predisposing disorder caused by pathogenic variants in the DICER1 gene
Gene: DICER1 PMCID: PMC7859642 PMID: 33552988 HGNCID: Unavailable Inheritance Pattern: Autosomal Dominant Disease Entity: familial pleuropulmonary blastoma (PPB),cystic nephroma, ovarian Sertoli-Leydig cell tumor (SLCT), multinodular goiter, cervix embryonal rhabdomyosarcoma, Wilms’ tumor, nasal chondromesenchymal hamartoma, ciliary body medulloepithelioma, differentiated thyroid carcinoma, pituitary blastoma, pineoblastoma, and sarcomas of different sites. Mutation: Germline Zygosity: Heterozygosity most common Variant: ClinVarID not available Family Information: No mention of disease within family Case: No case specified GnomAD: N/A Mutation Type: Nonsense or Frameshift
Tags
- nasal chondromesenchymal hamartoma
- FamilialPleuropulmonaryBlastoma
- cystic nephroma
- PMID: 33552988
- Cancer
- PMCID: PMC7859642
- pituitary blastoma
- NasalChondromesenchymalHamartoma
- HGNCID:Unavailable
- Pediatric
- Gene: DICER1
- Sarcomas
- AutosomalDominant
- Nonsense
- Zygosity: Heterosygosity
- Germline
- Wilms’ tumor
- CancerPredisposition
- CysticNephroma
- differentiated thyroid carcinoma
- multinodular goiter
- PPB
- familial pleuropulmonary blastoma
- sarcomas
- Heterozygosity
- Frameshift
- PMID:33552988
- SLCT
- ciliary body medulloepithelioma
- pineoblastoma
- Inheritance Pattern: Autosomal Dominant
- Mutation: Nonsense
- Mutation: Frameshift
- ovarian Sertoli-Leydig cell tumor
- cervix embryonal rhabdomyosarcoma
Annotators
URL
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