Skip to main content

Table 4 Diagnosis achieved using the NGS-LSD tool

From: Assessment of a targeted resequencing assay as a support tool in the diagnosis of lysosomal storage disorders

PC AO GDD IS GENE OMIM REF SEC NT CHANGE AA CH MT SS PP CS ZIG MD BA DIAGNOS
P1 2Y 10Y Mod CLN5 608102 NM_006493 c.335G > C/c.835G > A p.R112P/p.D279N 099/0.99 0/0.16 1/1 + HO + NA Finnish variant late infantile CLN
P2 4Y 4Y Mod CLN6 606725 NM_017882 c.794_796del p.S265del - - -   HO + NA Early juvenile late infantile CLN
P3 3Y 12Y High CLN3 607042 NM_000086 c.461-280_677 + 382del966 p.[Gly154Alafs*29, Val155_Gly264del] - - -   HO + NA Juvenile CLN
P4 2Y 21Y Mod MFSD8 611124 NM_152778 c.881C > A p. T294K 0.99 0 0.99 + HO + NA Turkish variant late infantile CLN
P5 4Y 12Y High CLN3 607042 NM_000086 c.371_372insT p.Y124fs - - -   HO - NA Juvenile CLN
P6 3Y 4.5Y High ARSA 607574 NM_000487 c.465 + 1G > A ---------- - - - + HO + + Metachromatic leukodystrophy
P7 1Y 8Y Low GLB1 611458 NM_000404 c.922 T > C p.F308L 0.99 0 1 + HO - + GM1 gangliosidosis
P8 3Y 1Y High HEXA 606869 NM_000520 c.533G > A p.R178H 0.99 0 1 + HO + + GM2 gangliosidosis, B1variant
P9 4Y 10Y Low HEXA 606869 NM_000520 c.1496G > A p.R499H 0.99 0 1   HT + + GM2 gangliosidosis, juvenil (TS)
     HEXA   NM_000520 c.1003A > T p.I335F 0.99 0 0.97   HT +   
P10 3Y 7Y High GLB1 611458 NM_000404 c.602G > A p.R201H 0.99 0.02 1   HT + + GM1 gangliosidosis
     GLB1   NM_000404 c.1188_1188dupG p.P397fs - - -   HT -   
P11 5Y 18Y High HEXA 606869 NM_000520 c.155C > A p.S52X - - - + HT + + GM2 gangliosidosis juvenile (TS)
     HEXA   NM_000520 c.1305C > T p.Y435Y - - -   HT -   
P12 13Y 6Y Low NPC2   NM_006432 c.441 + 1G > A ----------- - - -   HT - - Niemann-Pick disease, type C2?
P13 18 M 3Y High GNPTAB 607840 NM_024312 c.2354 T > G p.L785W 0.71 0.09 0.022 + HT - + Mucolipidosis II/III
     GNPTAB   NM_024312 c.1774G > A p.A592T 0.98 0.01 0.955   HT -   
P14 12 M 4Y High HEXA 606869 NM_000520 c.718_719insT p.K240fs      HT - + GM2 gangliosidosis (TS)
     HEXA   NM_000520 c.1003A > T p.I335F 0.99 0.00 0.467   HT +   
P15 0 M 1Y High GLB1 611458 NM_000404 c.671_672delAT p.H224Qfs     + HO - +* GM1 gangliosidosis
P16 9 M 1Y High ARSB 611542 NM_000046 c.382_384delCTC p.L128del      HO - +* Mucopolysaccharidosis VI
P17 0 M 3Y High GNPTAB 607840 NM_024312 c.3739_3742delCTTT p.E1248fs     + HO - + Mucolipidosis II/III
P18 2 M 6Y High IDS 300823 NM_000202 c.425C > T p.S142F 0.98 0.00 0.998 + HE + +* Hunter Syndrome
P19 3Y 5Y High IDUA 252800 NM_000203 c.1205G > A p.W402X     + HT + +* Hurler Syndrome
     IDUA   NM_000203 c.1874A > G p.Y625C 0.98 0.00 0.99   HT -   
P20 10 M 2Y High GLB1 611458 NM_000404 c.947A > G p.Y316C 0.999 0 0.79   HT + +* GM1 gangliosidosis
     GLB1   NM_000404 c.458-401_552 + 1033del1529 -----------      HT +   
P21 20 M 4Y High HEXA 606869 NM_000520 c.459 + 5G > A -----------      HT + +* GM2 gangliosidosis (TS)
     HEXA   NM_000520 c.533G > A p.R178H 0.99 0 1   HT +   
P22 2Y 4Y High CLN8 607837 NM_018941 c.509C > G p.T170R 0.999 0.00 0.999 + HO + NA Ceroid lipofuscinosis, neuronal, 8
P23 3Y 9Y High CTSD 116840 NM_001909 c.470C > T p.S157L 0.98 0.03 0.005 + HT - NA Ceroid lipofuscinosis, neuronal, 10
     CTSD   NM_001909 c.353-12G > A ----------- - - -   HT - pendε  
P24 3Y 23Y High HGSNAT 610453 NM_152419 c.1250 + 1G > A ----------- - - -   HT + +* Sanfilippo C
     HGSNAT   NM_152419 c.1270G > A p. G424S 0.999 0.59 1   HT +   
P25 1Y 6Y High GM2A 613109 NM_000405 c.333delC p. C112Vfs - - -   HO - +# GM2 gangliosidosis, AB variant
P26 4Y >20Y High CLN8 607837 NM_018941 c.792C > G p. N264K 0.97 0 0.99 + HO - NA Ceroid lipofuscinosis, neuronal, 8
  1. Notes and abbreviations: Samples from Patients P1-P12 were processed using SOLiD4 (Life Technologies), but those from P13-P26 using HiSeq2000 (Illumina); PC: Patient Code; AO: Age of Onset (Y: years; M: months); GDD: Genetic Diagnosis Delay (Y: years; M: months: DEC: deceased); IS: index of suspicion of LSD (Mod: moderate); REF SEC: reference sequence for which mutations are annotated; Nt and Aa Change: nucleotide and amino acid change (population frequency ≤0.01 according to 1000G2012 database); MT: Mutation Taster, SS: Sift Score and PP: Polyphen 2 score (in silico values to assess pathogenicity of missense variants); CS: Cosegregation; ZIG: zigosity; HO: homozygote; HT: heterozygote; HE: hemizygous; MD: Mutation description in Human Gene Mutation Database (+: previously associated with pathology; −: not previously associated); BA: Biochemical assay (+: positive; NA: test not available; −: negative); CLN: Neuronal Ceroid Lipofuscinosis; TS: Tay-Sachs; *Levels detected before NGS-LSD assay; εmRNA splicing analysis; #histopathology congruent with GM2 diagnosis.