Table 8. [Niemann-Pick Disease Type C: Notable Pathogenic Variants by Gene]. - GeneReviews®

Gene	Reference Sequences	DNA Nucleotide Change	Predicted Protein Change	Comment [Reference]
NPC1	NM_000271.3 NP_000262.1	c.530G>A	p.Cys177Tyr	Homozygotes have late-infantile NPC [Fernandez-Valero et al 2005].
c.1211G > A	p.Arg404Gln	Assoc'd in homozygous state w/early-onset pulmonary disease in Israel [Staretz-Chacham et al 2018].
c.2324A>C	p.Gln775Pro	Homozygotes have early-infantile NPC [Fernandez-Valero et al 2005].
c.2974G>T	p.Gly992Trp	Founder variant in Acadian population (Yarmouth County) of Nova Scotia [Winsor & Welch 1978, Greer et al 1998]
c.2974G>A	p.Gly992Arg	Described in France [Fernandez-Valero et al 2005]
c.3160G>A	p.Ala1054Thr	Assoc'd w/early-infantile NPC [Millat et al 2001]
c.3182T>C	p.Ile1061Thr	Accounts for 15%-20% of pathogenic variants in Western Europe & US [Millat et al 2005], ranging from 38% of affected persons in UK [Imrie et al 2015] to 3% of variants in an Italian study [Dardis et al 2020]
NPC2	NM_006432.3 NP_006423.1	c.115G>A	p.Val39Met	Adult-onset disease w/frontal lobe atrophy has been described [Klünemann et al 2002, Chikh et al 2005].
c.133C>T	p.Gln45Ter	Homozygotes have neonatal or infantile onset & die in early childhood [Chikh et al 2005].
c.141C>A	p.Cys47Ter
c.199T>C	p.Ser67Pro	Homozygotes survive into middle adulthood [Chikh et al 2005].
c.295T>C	p.Cys99Arg	Homozygotes have neonatal or infantile onset & die in early childhood [Chikh et al 2005].

Gene

Reference Sequences

DNA Nucleotide Change

Predicted Protein Change

Comment [Reference]

NPC1

NM_000271.3
NP_000262.1

c.530G>A

p.Cys177Tyr

Homozygotes have late-infantile NPC [Fernandez-Valero et al 2005].

c.1211G > A

p.Arg404Gln

Assoc'd in homozygous state w/early-onset pulmonary disease in Israel [Staretz-Chacham et al 2018].

c.2324A>C

p.Gln775Pro

Homozygotes have early-infantile NPC [Fernandez-Valero et al 2005].

c.2974G>T

p.Gly992Trp

Founder variant in Acadian population (Yarmouth County) of Nova Scotia [Winsor & Welch 1978, Greer et al 1998]

c.2974G>A

p.Gly992Arg

Described in France [Fernandez-Valero et al 2005]

c.3160G>A

p.Ala1054Thr

Assoc'd w/early-infantile NPC [Millat et al 2001]

c.3182T>C

p.Ile1061Thr

Accounts for 15%-20% of pathogenic variants in Western Europe & US [Millat et al 2005], ranging from 38% of affected persons in UK [Imrie et al 2015] to 3% of variants in an Italian study [Dardis et al 2020]

NPC2

NM_006432.3
NP_006423.1

c.115G>A

p.Val39Met

Adult-onset disease w/frontal lobe atrophy has been described [Klünemann et al 2002, Chikh et al 2005].

c.133C>T

p.Gln45Ter

Homozygotes have neonatal or infantile onset & die in early childhood [Chikh et al 2005].

c.141C>A

p.Cys47Ter

c.199T>C

p.Ser67Pro

Homozygotes survive into middle adulthood [Chikh et al 2005].

c.295T>C

p.Cys99Arg

Homozygotes have neonatal or infantile onset & die in early childhood [Chikh et al 2005].

From: Niemann-Pick Disease Type C

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