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Table 5 LIPA genotype (assessed by central laboratory)

From: Long-term survival with sebelipase alfa enzyme replacement therapy in infants with rapidly progressive lysosomal acid lipase deficiency: final results from 2 open-label studies

Study Patient # Allelic mutations Effects of mutation Variant severity
VITAL
  1 ND NA NA
  2 c.46A > C HOM C
c.676-42G > A HET
c.966 + 46C > T HET
c.894G > A HET
c.455 T > C HET
p.Thr16Pro rs1051338
Intronic rs1556478
Intronic rs3802656
p.Gln298Gln rs116928232
p.Leul52Pro
Common variant
Common variant
Common variant
Documented pathogenic
VUS
  3 c.884A > G HET p.His295Arg VUS
  4 c.539-5C > T HET
c.482delA HET
c.538G > A HET
Intronic rs2297472
p.Asn161Ilefs*19
p.Gly180Ser
Common variant
Documented pathogenic
VUS
  5 c.539-5C > T HET
c.676-42G > A HOM
c.966 + 46C > T HOM
c.193C > T HET
c.894G > A HET
c.419G > C HOM
Intronic rs2297472
Intronic rs1556478
Intronic rs3802656
p.Arg65Stop
p.Gln298Gln rs116928232
p.Trp140Ser
Common variant
Common variant
Common variant
Documented pathogenic
Documented pathogenic
VUS
  6 c.676-2A > G HOM Intronic Documented pathogenic
  7 c.350_351insCC HET
c.797G > T HET
p.Met117IlefsStop45
p.Gly266Val
Expected
Pathogenic VUS
  8 ND NA NA
  9 c.67G > A HOM
c.539-5C > T HET
c.260G > T HOM
p.Gly23Arg rs1051339
Intronic rs2297472
p.Gly87Val
Common variant
Common variant
Documented pathogenic
CL08
  1 c.594dupT HOM p.Ala199Cysfs*13 Documented pathogenic
  2a,b c.67G > A HOM
c.539-5C > T HOM
p.Gly23Arg
Intronic
Common variant
Common variant
  3 ND NA NA
  4 ND NA NA
  5a ND NA NA
  6a ND NA NA
  7 c.229G > T HOM Intronic Documented pathogenic
  8 ND NA NA
  9 c.46A > C HOM
c.658C > T HOM
c.539-5C > T HOM
c.894 + 1G > A HOM
p.Thr16Pro
p.Pro220Ser
Intronic
Splicing
Common variant
VUSc
Common variant
Documented pathogenic
  10 c.892C > Td p.Gln298* Documented pathogenic
  1. HET heterozygous, HOM homozygous, NA not applicable, ND not done, VUS variant of unknown significance
  2. aPatient was homozygous for whole LIPA deletion, including the neighboring gene for cholesterol 25-hydroxylase, CH25H, based on testing at a local laboratory
  3. bGene sequencing data from the central laboratory identified 2 polymorphisms, both common variants for the patient. It is recognized that the results from the central and local laboratories are discrepant, in that allelic variants should not have been detected in a patient who is homozygous for a whole LIPA deletion. Investigation into the cause of this discrepancy is ongoing
  4. cNovel missense mutation
  5. dThe testing laboratory did not report whether the patient was heterozygous or homozygous for the given allelic mutation; however, both parents were heterozygous for this mutation