TABLE 1.
Summary of biochemical, clinical, and molecular characteristics of the studied patients
| Patient | Biochemical Phenotype (Filipin) | Clinical subtype | Age at neurological onset (first symptoms) | Mutation | Protein | Location | Region affected | Reference | ||
|---|---|---|---|---|---|---|---|---|---|---|
| Group I | ||||||||||
| Patients analyzed by ngs |
Family 1 (F1) Portuguese |
P1 | Classical | Juvenile | 6 years |
c. 1514T>G c.1686G=A |
p.V505G/V562V a | Ex9/Ex11 | Luminal loop (between TM2 and TM3) | This work/(Fernandez‐Valero et al., 2005) |
| Tunisian Patient | P2 | n.a. | n.a. | n.a. |
c.7G=A/ c.2882A=G |
p.A3T/N961S | Ex1/Ex19 | N‐terminus/Cysteine‐rich luminal loop (between TM‐8 and TM‐9) | (Runz et al., 2008)/(Dvorakova et al., 2006) | |
| Group II | ||||||||||
| Revisited patients |
Family 2 (F2) Portuguese |
P3 (F2:1) |
Variant | Juvenile | 7 years |
c.1552C=T c.1686G=A |
p.R518W/V562V a | Ex9/Ex11 | Luminal loop (between TM‐2 and TM‐3) | (Ribeiro et al., 2001)/This work |
|
P3′ (F2:2) |
Variant | Juvenile | 7 years |
c.1552C=T c.1686G=A |
p.R518W/V562V a | Ex9/Ex11 | Luminal loop (between TM‐2 and TM‐3) | (Ribeiro et al., 2001)/This work | ||
| Group III | ||||||||||
| NPC patients (previously diagnosed) used in mars seq analysis as npc controls | P4 | Variant | Juvenile | 7 years |
c.2932C=T c.3662delT |
p.R978C/F1221fsX20 | Ex20/Ex24 | Cysteine‐rich luminal loop (between TM‐8 and TM‐9)/TM‐13; C‐terminus | (Ribeiro et al., 2001) | |
| P5 | Classical | Juvenile | 7 years |
c.1552C=T c.3104C=T |
p.R518W/A1035V | Ex9/Ex21 |
Luminal loop (between TM‐2 and TM‐3) Cysteine‐rich luminal loop (between TM‐8 and TM‐9) |
(Ribeiro et al., 2001) | ||
Patients P3 and P3′ are siblings.
GeneBank references: NPC1: NM_000271.5, Transcript ENST00000269228.10].
Abbreviations: Ex, exon; F, family; n.a., information not available; P, patient; TM, transmembrane.
a
Reclassified as a disease‐causing mutation (leads to exon skipping and premature stop codon).