47 Matching Annotations
  1. Last 7 days
    1. CaseMYH7-2: Australia

      DiseaseAssertion: Hypertrophic Cardiomyopathy

      FamilyInfo: N/A

      CasePresentingHPOs: HP:0001639 (Hypertrophic cardiomyopathy)

      HPOsFreeText: N/A

      CaseNotHPOs: N/A

      NotHPOsFreeText: N/A

      CaseAddInfo: N/A

      CasePreviousTesting: See Table 1

      CaseGenotypingMethod: DNA was isolated from peripheral blood. Most participants underwent testing from the Illumina Cardiomyopathy Sequencing Panel, which includes 46 cardiomyopathy related genes. For others, whole exome sequencing or Sanger squencing was used. After the results were returned, variants were filtered for pathogenicity and rarity.

      Variant: NM_000257.3:c.5287G>A (p.Ala1763Thr)

      ClinVar: 177846 https://www.ncbi.nlm.nih.gov/clinvar/variation/177846/

      gnomAD: European (Non-Finnish) 1.238e-4, Overall 7.423e-5 https://gnomad.broadinstitute.org/variant/14-23884476-C-T

    1. Patient 2

      Case2: Female, Iran, 18 mo (age at diagnosis)

      CasePresentingHPOs: HP:0003324, HP:0001254, HP:0004789, HP:0002039, HP:0002015, HP:0002098, HP:0001508, HP:0002360, HP:0001298 (generalized muscle weakness, lethargy, milk intolerance, anorexia, swallowing difficulty, breathing difficulties, failure to thrive, sleep disturbance, encephalopathy)

      HPOsFreeText: unspecified abnormalities in sitting and speech

      Case (Level 2)


      CasePreviousTesting: elevated propionylcarnitines (4.24 umol/L), Urine MMA (BT) 2200 umol/mmol creatinine, Urine MMA (AT) 40.0 umol/mmol creatinine

      CaseMethod1: same as group

      CaseGenotypingMethod: same as group


      Variant: NM_000255.3:c.2125-3C>G

      ClinVar: n/a

      CAID: CA913187295

      gnomAD: n/a


      CaseAddInfo: consanguineous parents. Treated for MMA with L-carnitine, biotin, and vitamin B12. Died at the age of 3.5 y. homozygous mutation.

    2. Patient 3

      Case3: Female, Iran, 3 d (age at diagnosis)

      CasePresentingHPOs: HP:0002883, HP:0001254, HP:0004789, HP:0002039, HP:0001290, HP:0001941, HP:0001508, HP:0001298, HP:0002019 (rapid breathing, lethargy, milk intolerance, anorexia, hypotonia, acidosis, failure to thrive, encephalopathy, constipation)

      Case (Level 2)


      CasePreviousTesting: elevated propionylcarnitine (61 umol/L), Urine MMA (BT) 1950 umol/mmol creatinine, Urine MMA (AT) 35.0 umol/mmol creatinine.

      CaseMethod1: same as group

      CaseGenotypingMethod: same as group


      Variant: NM_000255.3:c.2125-3C>G

      ClinVar: n/a

      CAID: CA913187295

      gnomAD: n/a


      CaseAddInfo: Consanguineous parents. Treated for MMA with L-carnitine, sodium benzoate, and vitamin B12. Currently 6 y, with moderately delayed development. Deceased infant sibling with similar symptoms, not genotyped. homozygous mutation.

    3. Three unrelated affected patients

      GroupPresentingHPOs: HP:0002013, HP:0001263 (vomiting, developmental delay)

      HPOsFreeText: increased urinary excretion of methylmalonate and methylcitric acids. Elevated propionylcarnitine.

      NumberMales: 0

      NumberFemales: 3

      CountryOrigin: Iran

      AgeRange: 3 d-22 mo (age at diagnosis)

      TotalNumber: 3

      FamilyInfo: 3

      NoFamily: 0

      GroupAddInfo: All probands are products of consanguineous marriages.

      Group (Level 2)


      VariantCount: 3

      NonVariant: 0

      OtherVariant: 0

      GroupPreviousTesting: urine organic acid analysis with urease treatment extraction with gas chromatography-mass spectrometry, after showing high levels of propionylcarnitine (umol/L) through tandem mass spectrometry

      GroupMethod1: PCR

      GroupGenotypingMethod: Genomic DNA was extracted from peripheral blood samples by the salting out method. MUT gene was analyzed by PCR and sequencing of both DNA strands of the entire coding region and highly-conserved exon-intron splice junctions. Reference sequence is NM_000255.3. Amplification was confirmed by electrophoresis, and products of the sequencing reaction were analyzed by DNA Sequencher 4.7. The phase of the mutation was confirmed by sequencing DNA from the patients parents.

    4. Patient 1

      Case1: Female, Iran, 22 mo (age at diagnosis)

      CasePresentingHPOs: HP:0001250, HP:0001290, HP:0001941, HP:0002019, HP:0002355, HP:0001344 (seizures, generalized hypotonia, acidosis, constipation, difficulty walking, absent speech)

      HPOsFreeText: congenital malformations

      Case (Level 2)


      CasePreviousTesting: elevation of propionylcarnitine (9.8 umol/L0, Urine MMA (BT) 2800 umol/mmol creatinine, Urine MMA (AT) 47.0 umol/mmol creatinine

      CaseMethod1: same as group

      CaseGenotypingMethod: same as group


      Variant: NM_000255.3:c.2125-3C>G

      ClinVar: n/a

      CAID: CA913187295

      gnomAD: n/a


      CaseAddInfo: consanguineous parents, treated for MMA with phenobarbital, L-carnitine, and vitamin B12. Died at 3 y of age. homozygous mutation.

    1. 48

      Case48: 8 mo (at biopsy), Indian

      Case 48 (Level 2)


      CasePreviousTesting: same as group. found 1.1 nmol/mg protein/18 h propionate incorporation, 1.1 nmol/mg/protein/18 h propionate incorporation with hydroxocobalamin supplementation

      CaseMethod1: same as group

      CaseMethod2: same as group

      CaseGenotypingMethod: same as group


      Variant1: NM_000255.3:c.2179C>T (p.Arg727Ter)

      ClinVar: 218998

      CAID: CA347913

      gnomAD: 0.0001504 (East Asian)


      CaseAddInfo: mut0 type, homozygous mutations.

    2. 47

      Case47: 2 y 7 mo (at biopsy), Barbadian

      Case 47 (Level 2)


      CasePreviousTesting: same as group. found 0.4 nmol/mg protein/18 h propionate incorporation, 1.3 nmol/mg/protein/18 h propionate incorporation with hydroxocobalamin supplementation

      CaseMethod1: same as group

      CaseMethod2: same as group

      CaseGenotypingMethod: same as group


      Variant1: NM_000255.3:c.2150G>T (p.Gly717Val)

      ClinVar: 1881

      CAID: CA249729

      gnomAD: 0.0006810 (African)


      CaseAddInfo: mut- type, homozygous mutations. reportedly non-consanguineous

    3. 46

      Case46: 1 y (at biopsy), White

      Case 46 (Level 2)


      CasePreviousTesting: same as group. found 1.0 nmol/mg protein/18 h propionate incorporation, 0.9 nmol/mg/protein/18 h propionate incorporation with hydroxocobalamin supplementation

      CaseMethod1: same as group

      CaseMethod2: same as group

      CaseGenotypingMethod: same as group


      Variant1: NM_000255.3:c.1962_1963delTC (p.Arg655Terfs)

      ClinVar: 552144

      CAID: CA658821515

      gnomAD: n/a


      CaseAddInfo: mut0 type, homozygous mutations.

    4. 44

      Case44: 13y (at biopsy), Arab

      Case 44 (Level 2)


      CasePreviousTesting: same as group. found 0.8 nmol/mg protein/18 h propionate incorporation, 1.1 nmol/mg/protein/18 h propionate incorporation with hydroxocobalamin supplementation

      CaseMethod1: same as group

      CaseMethod2: same as group

      CaseGenotypingMethod: same as group


      Variant1: NM_000255.3:c.1871A>G (p.Gln624Arg)

      ClinVar: n/a

      CAID: CA3846720

      gnomAD: 0.00003266 (South Asian)


      CaseAddInfo: mut0 type, homozygous mutations.

    5. 43

      Case43: 20 y (at biopsy), Lebanese

      Case 43 (Level 2)


      CasePreviousTesting: same as group. found 1.4 nmol/mg protein/18 h propionate incorporation, 1.1 nmol/mg/protein/18 h propionate incorporation with hydroxocobalamin supplementation

      CaseMethod1: same as group

      CaseMethod2: same as group

      CaseGenotypingMethod: same as group


      Variant1: NM_000255.3:c.1741C>T (p.Arg581Ter)

      ClinVar: 554675

      CAID: CA364395893

      gnomAD: n/a


      CaseAddInfo: mut0 type, homozygous mutations.

    6. 45

      Case45: no age or ethnicity recorded

      Case 45 (Level 2)


      CasePreviousTesting: same as group. found 1.5 nmol/mg protein/18 h propionate incorporation, 1.6 nmol/mg/protein/18 h propionate incorporation with hydroxocobalamin supplementation

      CaseMethod1: same as group

      CaseMethod2: same as group

      CaseGenotypingMethod: same as group


      Variant1: NM_000255.3:c.1891delG (p.Ala631GlinfsTer17)

      ClinVar: n/a

      CAID: CA351288

      gnomAD: 0.00002896 (Latino)


      CaseAddInfo: mut0 type, homozygous mutations.

    7. 42

      Case42: 1 y 7 mo (at biopsy), Hmong

      Case 42 (Level 2)


      CasePreviousTesting: same as group. found 4.5 nmol/mg protein/18 h propionate incorporation, 9.0 nmol/mg/protein/18 h propionate incorporation with hydroxocobalamin supplementation

      CaseMethod1: same as group

      CaseMethod2: same as group

      CaseGenotypingMethod: same as group


      Variant1: NM_000255.3:c.1663G>A (p.Ala555Thr)

      ClinVar: 203850

      CAID: CA312769

      gnomAD: 0.0003262 (East Asian)


      CaseAddInfo: mut- type, homozygous mutations. Additional heterozygous mutations in CUBN gene (Variant 1: NM_001081.3:c.3500G>T, CAID: CA376148913 , gnomAD: 0.00005014, East Asian ) (Variant 2: NM_001081.3:c.6211A>G, CAID: CA5423765 , gnomAD: 0.001003, East Asian )

    8. 41

      Case41: 6 mo (at biopsy), Pakistani

      Case 41 (Level 2)


      CasePreviousTesting: same as group. found 0.6 nmol/mg protein/18 h propionate incorporation, 0.6 nmol/mg/protein/18 h propionate incorporation with hydroxocobalamin supplementation

      CaseMethod1: same as group

      CaseMethod2: same as group

      CaseGenotypingMethod: same as group


      Variant1: NM_000255.3:c.1560G>C (p.Lys520Asn)

      ClinVar: n/a

      CAID: CA364397073

      gnomAD: n/a


      CaseAddInfo: mut0 type, homozygous mutations.

    9. 40

      Case40: Middle Eastern

      Case 40 (Level 2)


      CasePreviousTesting: same as group. found 1.8 nmol/mg protein/18 h propionate incorporation, 1.6 nmol/mg/protein/18 h propionate incorporation with hydroxocobalamin supplementation

      CaseMethod1: same as group

      CaseMethod2: same as group

      CaseGenotypingMethod: same as group


      Variant1: NM_000255.3:c.1420C>T (p.Arg474Ter)

      ClinVar: 554873

      CAID: CA138795916

      gnomAD: 0.00003267 (South Asian)


      CaseAddInfo: mut0 type, homozygous mutations. documented consanguinity.

    10. 39

      Case39: 1 y (at biopsy), Asian

      Case 39 (Level 2)


      CasePreviousTesting: same as group. found 1.4 nmol/mg protein/18 h propionate incorporation, 1.5 nmol/mg/protein/18 h propionate incorporation with hydroxocobalamin supplementation

      CaseMethod1: same as group

      CaseMethod2: same as group

      CaseGenotypingMethod: same as group


      Variant1: NM_000255.3:c.1280G>A (p.Gly427Asp)

      ClinVar: 218990

      CAID: CA347873

      gnomAD: 0.0004011 (East Asian)


      CaseAddInfo: mut0 type, homozygous mutations. documented non-consanguinity.

    11. 38

      Case38: 9 y (at biopsy), German/Polish

      Case 38 (Level 2)


      CasePreviousTesting: same as group. found 0.5 nmol/mg protein/18 h propionate incorporation, 0.5 nmol/mg/protein/18 h propionate incorporation with hydroxocobalamin supplementation

      CaseMethod1: same as group

      CaseMethod2: same as group

      CaseGenotypingMethod: same as group


      Variant1: NM_000255.3:c.1106G>A (p.Arg369His)

      ClinVar: 203846

      CAID: CA312764

      gnomAD: 0.0001504 (East Asian)


      CaseAddInfo: mut0 type, homozygous mutations.

    12. 37

      Case37: 18 mo (at biopsy), Moroccan

      Case 37 (Level 2)


      CasePreviousTesting: same as group. found 0.5 nmol/mg protein/18 h propionate incorporation, 0.5 nmol/mg/protein/18 h propionate incorporation with hydroxocobalamin supplementation

      CaseMethod1: same as group

      CaseMethod2: same as group

      CaseGenotypingMethod: same as group


      Variant1: NM_000255.3:c.683G>A (p.Arg228Gln)

      ClinVar: n/a

      CAID: CA3847070

      gnomAD: 0.00002905 (Latino)


      CaseAddInfo: mut0 type, homozygous mutations.

    13. 36

      Case36: 14 mo (at biopsy), Hispanic

      Case 36 (Level 2)


      CasePreviousTesting: same as group. found 0.7 nmol/mg protein/18 h propionate incorporation, 0.8 nmol/mg/protein/18 h propionate incorporation with hydroxocobalamin supplementation

      CaseMethod1: same as group

      CaseMethod2: same as group

      CaseGenotypingMethod: same as group


      Variant1: NM_000255.3:c.406G>T (p.Val136Phe)

      ClinVar: n/a

      CAID: CA364404792

      gnomAD: n/a


      CaseAddInfo: mut0 type, homozygous mutations. documented consanguinity.

    14. 35

      Case35: 5 y (at biopsy), Hispanic

      Case 35 (Level 2)


      CasePreviousTesting: same as group. found 0.5 nmol/mg protein/18 h propionate incorporation, 0.7 nmol/mg/protein/18 h propionate incorporation with hydroxocobalamin supplementation

      CaseMethod1: same as group

      CaseMethod2: same as group

      CaseGenotypingMethod: same as group


      Variant1: NM_000255.3:c.322C>T (p.Arg108Cys)

      ClinVar: 1887

      CAID: CA249732

      gnomAD: 0.0008393 (Latino)


      CaseAddInfo: mut0 type, homozygous mutations.

    15. 33

      Case33: 9 mo (at biopsy), Hispanic

      Case 33 (Level 2)


      CasePreviousTesting: same as group. found 1.0 nmol/mg protein/18 h propionate incorporation, 1.3 nmol/mg/protein/18 h propionate incorporation with hydroxocobalamin supplementation

      CaseMethod1: same as group

      CaseMethod2: same as group

      CaseGenotypingMethod: same as group


      Variant1: NM_000255.3:c.322C>T (p.Arg108Cys)

      ClinVar: 1887

      CAID: CA249732

      gnomAD: 0.0008393 (Latino)


      CaseAddInfo: mut0 type, homozygous mutations.

    16. 32

      Case32: 10 y (at biopsy), Arab

      Case 32 (Level 2)


      CasePreviousTesting: same as group. found 1.0 nmol/mg protein/18 h propionate incorporation, 1.0 nmol/mg/protein/18 h propionate incorporation with hydroxocobalamin supplementation

      CaseMethod1: same as group

      CaseMethod2: same as group

      CaseGenotypingMethod: same as group


      Variant1: NM_000255.3:c.278G>A (p.Arg93His)

      ClinVar: 1880

      CAID: CA249728

      gnomAD: 0.0004777 (European- Finnish)


      CaseAddInfo: mut0 type, homozygous mutations. documented consanguinity.

    17. 34

      Case34: 3.5 wks (at biopsy), White/Hispanic

      Case 34 (Level 2)


      CasePreviousTesting: same as group. found 1.6 nmol/mg protein/18 h propionate incorporation, 1.8 nmol/mg/protein/18 h propionate incorporation with hydroxocobalamin supplementation

      CaseMethod1: same as group

      CaseMethod2: same as group

      CaseGenotypingMethod: same as group


      Variant1: NM_000255.3:c.322C>T (p.Arg108Cys)

      ClinVar: 1887

      CAID: CA249732

      gnomAD: 0.0008393 (Latino)


      CaseAddInfo: mut0 type, homozygous mutations.

    18. 43

      Case43: 20 y (at biopsy), Lebanese

      Case 43 (Level 2)


      CasePreviousTesting: same as group. found 1.4 nmol/mg protein/18 h propionate incorporation, 1.1 nmol/mg/protein/18 h propionate incorporation with hydroxocobalamin supplementation

      CaseMethod1: same as group

      CaseMethod2: same as group

      CaseGenotypingMethod: same as group


      Variant1: NM_000255.3:c.1741C>T (p.Arg581Ter)

      ClinVar: 554675

      CAID: CA364395893

      gnomAD: n/a


      CaseAddInfo: mut0 type, homozygous mutations.

    19. 45

      Case45: no age or ethnicity recorded

      Case 45 (Level 2)


      CasePreviousTesting: same as group. found 1.5 nmol/mg protein/18 h propionate incorporation, 1.6 nmol/mg/protein/18 h propionate incorporation with hydroxocobalamin supplementation

      CaseMethod1: same as group

      CaseMethod2: same as group

      CaseGenotypingMethod: same as group


      Variant1: NM_000255.3:c.1891delG (p.Ala631GlinfsTer17)

      ClinVar: n/a

      CAID: CA351288

      gnomAD: 0.00002896 (Latino)


      CaseAddInfo: mut0 type, homozygous mutations.

    20. 42

      Case42: 1 y 7 mo (at biopsy), Hmong

      Case 42 (Level 2)


      CasePreviousTesting: same as group. found 4.5 nmol/mg protein/18 h propionate incorporation, 9.0 nmol/mg/protein/18 h propionate incorporation with hydroxocobalamin supplementation

      CaseMethod1: same as group

      CaseMethod2: same as group

      CaseGenotypingMethod: same as group


      Variant1: NM_000255.3:c.1663G>A (p.Ala555Thr)

      ClinVar: 203850

      CAID: CA312769

      gnomAD: 0.0003262 (East Asian)


      CaseAddInfo: mut- type, homozygous mutations. Additional heterozygous mutations in CUBN gene (Variant 1: NM_001081.3:c.3500G>T, CAID: CA376148913 , gnomAD: 0.00005014, East Asian ) (Variant 2: NM_001081.3:c.6211A>G, CAID: CA5423765 , gnomAD: 0.001003, East Asian )

    21. 41

      Case41: 6 mo (at biopsy), Pakistani

      Case 41 (Level 2)


      CasePreviousTesting: same as group. found 0.6 nmol/mg protein/18 h propionate incorporation, 0.6 nmol/mg/protein/18 h propionate incorporation with hydroxocobalamin supplementation

      CaseMethod1: same as group

      CaseMethod2: same as group

      CaseGenotypingMethod: same as group


      Variant1: NM_000255.3:c.1560G>C (p.Lys520Asn)

      ClinVar: n/a

      CAID: CA364397073

      gnomAD: n/a


      CaseAddInfo: mut0 type, homozygous mutations.

    22. 40

      Case40: Middle Eastern

      Case 40 (Level 2)


      CasePreviousTesting: same as group. found 1.8 nmol/mg protein/18 h propionate incorporation, 1.6 nmol/mg/protein/18 h propionate incorporation with hydroxocobalamin supplementation

      CaseMethod1: same as group

      CaseMethod2: same as group

      CaseGenotypingMethod: same as group


      Variant1: NM_000255.3:c.1420C>T (p.Arg474Ter)

      ClinVar: 554873

      CAID: CA138795916

      gnomAD: 0.00003267 (South Asian)


      CaseAddInfo: mut0 type, homozygous mutations. documented consanguinity.

    23. 39

      Case39: 1 y (at biopsy), Asian

      Case 39 (Level 2)


      CasePreviousTesting: same as group. found 1.4 nmol/mg protein/18 h propionate incorporation, 1.5 nmol/mg/protein/18 h propionate incorporation with hydroxocobalamin supplementation

      CaseMethod1: same as group

      CaseMethod2: same as group

      CaseGenotypingMethod: same as group


      Variant1: NM_000255.3:c.1280G>A (p.Gly427Asp)

      ClinVar: 218990

      CAID: CA347873

      gnomAD: 0.0004011 (East Asian)


      CaseAddInfo: mut0 type, homozygous mutations. documented non-consanguinity.

    24. 38

      Case38: 9 y (at biopsy), German/Polish

      Case 38 (Level 2)


      CasePreviousTesting: same as group. found 0.5 nmol/mg protein/18 h propionate incorporation, 0.5 nmol/mg/protein/18 h propionate incorporation with hydroxocobalamin supplementation

      CaseMethod1: same as group

      CaseMethod2: same as group

      CaseGenotypingMethod: same as group


      Variant1: NM_000255.3:c.1106G>A (p.Arg369His)

      ClinVar: 203846

      CAID: CA312764

      gnomAD: 0.0001504 (East Asian)


      CaseAddInfo: mut0 type, homozygous mutations.

    25. 37

      Case37: 18 mo (at biopsy), Moroccan

      Case 37 (Level 2)


      CasePreviousTesting: same as group. found 0.5 nmol/mg protein/18 h propionate incorporation, 0.5 nmol/mg/protein/18 h propionate incorporation with hydroxocobalamin supplementation

      CaseMethod1: same as group

      CaseMethod2: same as group

      CaseGenotypingMethod: same as group


      Variant1: NM_000255.3:c.683G>A (p.Arg228Gln)

      ClinVar: n/a

      CAID: CA3847070

      gnomAD: 0.00002905 (Latino)


      CaseAddInfo: mut0 type, homozygous mutations.

    26. 36

      Case36: 14 mo (at biopsy), Hispanic

      Case 36 (Level 2)


      CasePreviousTesting: same as group. found 0.7 nmol/mg protein/18 h propionate incorporation, 0.8 nmol/mg/protein/18 h propionate incorporation with hydroxocobalamin supplementation

      CaseMethod1: same as group

      CaseMethod2: same as group

      CaseGenotypingMethod: same as group


      Variant1: NM_000255.3:c.406G>T (p.Val136Phe)

      ClinVar: n/a

      CAID: CA364404792

      gnomAD: n/a


      CaseAddInfo: mut0 type, homozygous mutations. documented consanguinity.

    27. 35

      Case35: 5 y (at biopsy), Hispanic

      Case 35 (Level 2)


      CasePreviousTesting: same as group. found 0.5 nmol/mg protein/18 h propionate incorporation, 0.7 nmol/mg/protein/18 h propionate incorporation with hydroxocobalamin supplementation

      CaseMethod1: same as group

      CaseMethod2: same as group

      CaseGenotypingMethod: same as group


      Variant1: NM_000255.3:c.322C>T (p.Arg108Cys)

      ClinVar: 1887

      CAID: CA249732

      gnomAD: 0.0008393 (Latino)


      CaseAddInfo: mut0 type, homozygous mutations.

    28. 33

      Case33: 9 mo (at biopsy), Hispanic

      Case 33 (Level 2)


      CasePreviousTesting: same as group. found 1.0 nmol/mg protein/18 h propionate incorporation, 1.3 nmol/mg/protein/18 h propionate incorporation with hydroxocobalamin supplementation

      CaseMethod1: same as group

      CaseMethod2: same as group

      CaseGenotypingMethod: same as group


      Variant1: NM_000255.3:c.322C>T (p.Arg108Cys)

      ClinVar: 1887

      CAID: CA249732

      gnomAD: 0.0008393 (Latino)


      CaseAddInfo: mut0 type, homozygous mutations.

    29. 32

      Case32: 10 y (at biopsy), Arab

      Case 32 (Level 2)


      CasePreviousTesting: same as group. found 1.0 nmol/mg protein/18 h propionate incorporation, 1.0 nmol/mg/protein/18 h propionate incorporation with hydroxocobalamin supplementation

      CaseMethod1: same as group

      CaseMethod2: same as group

      CaseGenotypingMethod: same as group


      Variant1: NM_000255.3:c.278G>A (p.Arg93His)

      ClinVar: 1880

      CAID: CA249728

      gnomAD: 0.0004777 (European- Finnish)


      CaseAddInfo: mut0 type, homozygous mutations. documented consanguinity.

    30. 34

      Case34: 3.5 wks (at biopsy), White/Hispanic

      Case 34 (Level 2)


      CasePreviousTesting: same as group. found 1.6 nmol/mg protein/18 h propionate incorporation, 1.8 nmol/mg/protein/18 h propionate incorporation with hydroxocobalamin supplementation

      CaseMethod1: same as group

      CaseMethod2: same as group

      CaseGenotypingMethod: same as group


      Variant1: NM_000255.3:c.322C>T (p.Arg108Cys)

      ClinVar: 1887

      CAID: CA249732

      gnomAD: 0.0008393 (Latino)


      CaseAddInfo: mut0 type, homozygous mutations.

    1. 43 patients

      GroupPresentingHPOs: HP:0001987, HP:0001942, HP:0003128, HP:0002912 (hyperammonemia, metabolic acidosis, lactic acidosis, methylmalonic acidemia)

      HPOsFreeText: elevated blood levels of propionylcarnitine (C3) (median 13.56 umol/L), and elevated C3 to acetylcarnitine (C2) ratio (median 0.85). elevated urine methylmalonate levels (median 598.96 mmol/mol creatinine). 28/73.7% displayed recurrent vomiting (HP:0002572). 28/73.7% displayed disturbances of consciousness (HP:0004372). 23/60.5% displayed feeding difficulties in infancy (HP:0008872), 20/52.6% displayed respiratory distress (HP:0002098), 20/52.6% displayed failure to thrive (HP:0001508), 20/52.6% displayed dystonia (HP:0001332), 14/36.8% displayed mental retardation, 12/31.6% displayed convulsions.

      GroupNotHPOs: normal plasma total homocysteine

      NotHPOsFreeText:

      NumberMales: 27

      NumberFemales: 16

      CountryOrigin: China

      Ethnicity: Chinese

      AgeRange: 33d- 10.3 y at last follow up

      TotalNumber 43

      FamilyInfo: 43

      NoFamily: 0

      GroupAddInfo: 9 identified by NBS, 34 recruited after being suspected of inherited metabolism disorders. 42 families from 14 provinces of the Mainland of China. 8 died during acute metabolic crisis, 7 lost to follow up, 28 alive at end of study.

      Group (Level 2)


      VariantCount: 43 (35 had two mutant alleles)

      NonVariant: 0

      OtherVariant: 0

      GroupPreviousTesting: tandem mass spectrometry for blood levels, gas chromatography-mass spectrometry for urine,

      GroupMethod1: PCR

      GroupGenotypingMethod: genomic DNA extracted from peripheral blood leukocytes from patients and their parents. Exonic and flanking intronic regions of the MUT gene were amplified through PCR. PCR products were sequenced directly using forward and reverse primers on ABI 3700 sequencer. Mutation analysis using MUT reference NM_000255.3. Nucleotide numbering reflects cDNA numbering (initiation codon= codon1). All detected mutations were confirmed in the patients' parents. Novel variants were screened in 100 alleles from 50 control children. Novel variants were considered pathogenic when predicted to be deleterious by two algorithms.

    2. P1

      Case1: Male, Chinese, 11 mo (at end of study)

      Case1HPOs: HP:0012736 (profound psychomotor retardation)

      HPOsFreeText: 10 mo at onset, poor neurological outcome

      NotHPOsFreeText: not responsive to vitamin B12


      Case1 (Level 2)

      CasePreviousTesting: same as group

      CaseMethod1: same as group

      CaseMethod2: same as group

      CaseGenotypingMethod: same as group


      Variant: NM_000255.3(MMUT):c.323G>A (p.Arg108His)

      ClinVar: 100707

      CAID: CA235522

      gnomAD: 0.00006152 (African)


      CaseAddInfo: homozygous mutations

    3. P4

      Case4: Male, Chinese, 2.8 y (end of study)

      HPOsFreeText: poor neurologic outcome, neonatal onset

      NotHPOsFreeText: not responsive to vitamin B12


      Case4 (Level 2):

      CasePreviousTesting: NBS

      CaseMethod1: same as group

      CaseMethod2: same as group

      CaseGenotypingMethod: same as group


      Variant: NM_000255.3:c.729_730insTT (p.Asp244LeufsTer?)

      ClinVar: 552079

      CAID: CA3847064

      gnomAD: 0.0002008 (East Asian)


      CaseAddInfo: homozygous mutations

    4. P5

      Case5: Female, Chinese, 1.6 y (onset)

      HPOsFreeText: 1.6 y onset

      NotHPOsFreeText: Not responsive to vitamin B12


      Case5 (Level 2):

      CasePreviousTesting: same as group

      CaseMethod1: same as group

      CaseMethod2: same as group

      CaseGenotypingMethod: same as group


      Variant: NM_000255.3:c.1106G>A (p.Arg369His)

      ClinVar: 203846

      CAID: CA312764

      gnomAD: 0.0001504 (East Asian)


      CaseAddInfo: homozygous mutations, lost to follow up

    5. P3

      Case3: Female, Chinese, 4 mo (end of study)

      HPOsFreeText: Responsive to vitamin B12


      Case3 (Level 2):

      CasePreviousTesting: NBS

      CaseMethod1: same as group

      CaseMethod2: same as group

      CaseGenotypingMethod: same as group


      Variant: NM_000255.3:c.599T>C (p.Ille200Thr)

      ClinVar: n/a

      CAID: CA364404381

      gnomAD: n/a


      CaseAddInfo: homozygous mutations, asymptomatic

    6. P2

      Case2: Male, Chinese, 3 mo (age at death)

      HPOsFreeText: Neonatal onset

      NotHPOsFreeText: Not responsive to vitamin B12


      Case2 (Level 2):

      CasePreviousTesting: NBS (newborn screening)

      CaseMethod1: same as group

      CaseMethod2: same as group

      CaseGenotypingMethod: same as group


      Variant: NM_000255.3:c.482G>T (p.Gly161Val)

      ClinVar: n/a

      CAID: CA364404636

      gnomAD: n/a


      CaseAddInfo: homozygous mutations, novel mutation

    7. 43 patients

      GroupPresentingHPOs: HP:0001987, HP:0001942, HP:0003128, HP:0002912 (hyperammonemia, metabolic acidosis, lactic acidosis, methylmalonic acidemia)

      HPOsFreeText: elevated blood levels of propionylcarnitine (C3) (median 13.56 umol/L), and elevated C3 to acetylcarnitine (C2) ratio (median 0.85). elevated urine methylmalonate levels (median 598.96 mmol/mol creatinine). 28/73.7% displayed recurrent vomiting (HP:0002572). 28/73.7% displayed disturbances of consciousness (HP:0004372). 23/60.5% displayed feeding difficulties in infancy (HP:0008872), 20/52.6% displayed respiratory distress (HP:0002098), 20/52.6% displayed failure to thrive (HP:0001508), 20/52.6% displayed dystonia (HP:0001332), 14/36.8% displayed mental retardation, 12/31.6% displayed convulsions.

      GroupNotHPOs: normal plasma total homocysteine

      NotHPOsFreeText:

      NumberMales: 27

      NumberFemales: 16

      CountryOrigin: China

      Ethnicity: Chinese

      AgeRange: 33d- 10.3 y at last follow up

      TotalNumber 43

      FamilyInfo: 43

      NoFamily: 0

      GroupAddInfo: 9 identified by NBS, 34 recruited after being suspected of inherited metabolism disorders. 42 families from 14 provinces of the Mainland of China. 8 died during acute metabolic crisis, 7 lost to follow up, 28 alive at end of study.

      Group (Level 2)


      VariantCount: 43 (35 had two mutant alleles)

      NonVariant: 0

      OtherVariant: 0

      GroupPreviousTesting: tandem mass spectrometry for blood levels, gas chromatography-mass spectrometry for urine,

      GroupMethod1: PCR

      GroupGenotypingMethod: genomic DNA extracted from peripheral blood leukocytes from patients and their parents. Exonic and flanking intronic regions of the MUT gene were amplified through PCR. PCR products were sequenced directly using forward and reverse primers on ABI 3700 sequencer. Mutation analysis using MUT reference NM_000255.3. Nucleotide numbering reflects cDNA numbering (initiation codon= codon1). All detected mutations were confirmed in the patients' parents. Novel variants were screened in 100 alleles from 50 control children. Novel variants were considered pathogenic when predicted to be deleterious by two algorithms.

    8. P1

      Case1: Male, Chinese, 11 mo (at end of study)

      Case1HPOs: HP:0012736 (profound psychomotor retardation)

      HPOsFreeText: 10 mo at onset, poor neurological outcome

      NotHPOsFreeText: not responsive to vitamin B12


      Case1 (Level 2)

      CasePreviousTesting: same as group

      CaseMethod1: same as group

      CaseMethod2: same as group

      CaseGenotypingMethod: same as group


      Variant: NM_000255.3(MMUT):c.323G>A (p.Arg108His)

      ClinVar: 100707

      CAID: CA235522

      gnomAD: 0.00006152 (African)


      CaseAddInfo: homozygous mutations

    9. P4

      Case4: Male, Chinese, 2.8 y (end of study)

      HPOsFreeText: poor neurologic outcome, neonatal onset

      NotHPOsFreeText: not responsive to vitamin B12


      Case4 (Level 2):

      CasePreviousTesting: NBS

      CaseMethod1: same as group

      CaseMethod2: same as group

      CaseGenotypingMethod: same as group


      Variant: NM_000255.3:c.729_730insTT (p.Asp244LeufsTer?)

      ClinVar: 552079

      CAID: CA3847064

      gnomAD: 0.0002008 (East Asian)


      CaseAddInfo: homozygous mutations

    10. P5

      Case5: Female, Chinese, 1.6 y (onset)

      HPOsFreeText: 1.6 y onset

      NotHPOsFreeText: Not responsive to vitamin B12


      Case5 (Level 2):

      CasePreviousTesting: same as group

      CaseMethod1: same as group

      CaseMethod2: same as group

      CaseGenotypingMethod: same as group


      Variant: NM_000255.3:c.1106G>A (p.Arg369His)

      ClinVar: 203846

      CAID: CA312764

      gnomAD: 0.0001504 (East Asian)


      CaseAddInfo: homozygous mutations, lost to follow up

    11. P3

      Case3: Female, Chinese, 4 mo (end of study)

      HPOsFreeText: Responsive to vitamin B12


      Case3 (Level 2):

      CasePreviousTesting: NBS

      CaseMethod1: same as group

      CaseMethod2: same as group

      CaseGenotypingMethod: same as group


      Variant: NM_000255.3:c.599T>C (p.Ille200Thr)

      ClinVar: n/a

      CAID: CA364404381

      gnomAD: n/a


      CaseAddInfo: homozygous mutations, asymptomatic

    12. P2

      Case2: Male, Chinese, 3 mo (age at death)

      HPOsFreeText: Neonatal onset

      NotHPOsFreeText: Not responsive to vitamin B12


      Case2 (Level 2):

      CasePreviousTesting: NBS (newborn screening)

      CaseMethod1: same as group

      CaseMethod2: same as group

      CaseGenotypingMethod: same as group


      Variant: NM_000255.3:c.482G>T (p.Gly161Val)

      ClinVar: n/a

      CAID: CA364404636

      gnomAD: n/a


      CaseAddInfo: homozygous mutations, novel mutation