An uncommon inheritance pattern in Niemann-Pick disease type C: identification of probable paternal germline mosaicism in a Mexican family

Table 1 Comparison of the clinical characteristics and genotypes of previously reported patients who share at least one mutation with the present case

	Present case	Meiner et al. 2001 [5]	Xiong et al. 2012 [6]	Jahnova et al. 2014 [7]			Piña et al. 2014 [8]
Case	1	2	3	4	5	6	7
Age at onset	9 years	20 years	8.5 years	14 years (sibling of cases 5 and 6)	27 years (sibling of cases 4 and 6)	20 years (sibling of cases 4 and 5)	24 years
Gender	Male	Male	Male	Male	Female	Female	Female
Family consanguinity	-	+	-	-	-	-	-
Progressive clumsiness	+	-	+	-	-	-	+
VSGP	+	+	-	-	-	-	+
Dysarthria	+	+	+	+	-	-	-
Cataplexy	+	-	-	-	-	-	-
Ataxia	+	+	+	-	-	-	+
Splenomegaly	+	+	-	+	+	+	+
Cerebellar atrophy	-	NR	+	NR	NR	NR	+
Behavioral anomalies	+	-	-	+	+	+	+
Depression	-	-	-	-	+	-	+
Schizophrenia	-	-	-	-	-	+	+
Bone marrow aspiration	Blue histiocytes	Blue histiocytes	Blue histiocytes	NR	Blue histiocytes	NR	Foamy histiocytes
NP-C index suspicion score [11] at diagnosis	142 points	NR	NR	NR	NR	NR	227 points
Filipin staining	“Variant”^a	Positive	Not performed	“Variant”^a	“Variant”^a	“Variant”^a	Positive
NPC1 genotype	c.[1042C > T];[2780C > T] or p.[Arg348*];[Ala927Val]	c.[2780C > T];[2780C > T] or p.[Ala927Val];[Ala927Val]	c.[2777C > T];[2780C > T] or p.[Ala926Val];[Ala927Val]	c.[2780C > T];[2780C > T] or p.[Ala927Val];[Ala927Val]	c.[2780C > T];[2780C > T] or p.[Ala927Val];[Ala927Val]	c.[2780C > T];[2780C > T] or p.[Ala927Val];[Ala927Val]	c.[1042C > T];[3493G > A] or p.[Arg348*];[Val1165Met]
Family NPC1 studies	Mother and healthy sister: obligate p.(Ala927Val) and p.(Arg348) carriers, respectively Father: germline mosaicism for c.1042C > T (p.Arg348) variant	NR	NR	NR	NR	NR	NR

^aThe “variant” filipin fibroblast profile of NP-C refers to situations in which supplementation with pure low-density lipoproteins yields a less intense and non-uniform pattern of perinuclear fluorescent vesicles in cells. This phenotype makes it impossible to establish an accurate percentage of NP-C “positive” cells. Moreover, the presence of these “variant” phenotype cells within total human serum causes the filipin staining pattern to overlap even further with the normal to very mildly abnormal perinuclear fluorescent vesicle distribution characteristic of NP-C [4]
Abbreviations: NR not reported, VSGP vertical supranuclear gaze paralysis, (+) present, and (-) absent

ISSN: 1471-2377