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Clinical and genetic characteristics of mexican patients with juvenile presentation of niemann-pick type C disease.

Piña-Aguilar RE, Vera-Loaiza A, Chacón-Camacho OF, Zenteno JC, Nuñez-Orozco L, Santillán-Hernández Y - Case Rep Neurol Med (2014)

Bottom Line: Mexican patients with juvenile NPC presented with a variable clinical phenotype and compound heterozygosity.This suggests a relative high frequency of mutation carriers as it is reported for European population.Consequently, clinicians should consider NPC as a diagnosis possibility in any adolescent or young adult patient with juvenile dementia and/or ataxia, even in absence of gelastic cataplexy and supranuclear vertical gaze palsy.

View Article: PubMed Central - PubMed

Affiliation: Department of Medical Genetics, Centro Médico Nacional "20 de Noviembre", ISSSTE, San Lorenzo No. 502E, Colonia del Valle Sur, Del. Benito Juárez, 03100 México, DF, Mexico.

ABSTRACT
Niemann-Pick type C disease (NPC) is a rare lysosomal disease with a protean presentation, ranging from a fatal neonatal course with visceromegaly to an adult presentation with only neurological or psychiatric symptomatology. In this report we describe the genetic and clinical characteristics of 3 Mexican patients from different families with juvenile presentation of NPC. Clinical examination, imaging of central nervous and gastrointestinal system, and EEG were performed. Genetic studies include sequencing and deletion/duplication analysis of NPC1 and NPC2 genes. All patients presented with cognitive impairment, ataxia, and supranuclear vertical gaze palsy; one case had gelastic cataplexy. Also they developed epilepsy and cortical atrophy and two patients had thinning of corpus callosum. The 3 patients were compound heterozygotes for NPC1 sequence variants, including 5 missense and 1 nonsense mutations: p.P1007A and p.F1087L in Case 1; p.Q921P and p.G992R in Case 2; and p.R348∗ and p.V1165M in case 3. Mexican patients with juvenile NPC presented with a variable clinical phenotype and compound heterozygosity. This suggests a relative high frequency of mutation carriers as it is reported for European population. Consequently, clinicians should consider NPC as a diagnosis possibility in any adolescent or young adult patient with juvenile dementia and/or ataxia, even in absence of gelastic cataplexy and supranuclear vertical gaze palsy.

No MeSH data available.


Related in: MedlinePlus

Families' pedigrees of Case 1 (a), Case 2 (d), and Case 3 (g), showing the mutations found. Partial DNA sequence of NPC1 gene of Case 1 showing the p.P1007A mutation in exon 20 (b) and p.F1087L mutation in exon 22 (c). Partial DNA sequence of NPC1 gene of Case 2 demonstrating p.Q921P mutation in exon 18 (e) and p.G992R mutation in exon 20 (f). Partial DNA sequence of NPC1 gene of Case 3 demonstrating p.R348∗ in exon 8 (h) and p.V1165M in exon 23 (i). NA: not available.
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fig2: Families' pedigrees of Case 1 (a), Case 2 (d), and Case 3 (g), showing the mutations found. Partial DNA sequence of NPC1 gene of Case 1 showing the p.P1007A mutation in exon 20 (b) and p.F1087L mutation in exon 22 (c). Partial DNA sequence of NPC1 gene of Case 2 demonstrating p.Q921P mutation in exon 18 (e) and p.G992R mutation in exon 20 (f). Partial DNA sequence of NPC1 gene of Case 3 demonstrating p.R348∗ in exon 8 (h) and p.V1165M in exon 23 (i). NA: not available.

Mentions: Sequencing analysis showed heterozygous missense changes in NPC1, one in exon 20 c.3019C>G (p.P1007A) and the other in exon 22, c.3259T>C (p.F1087L). Neither mutations in NPC2 nor gross deletion/duplications in NPC1 or NPC2 were detected. Mutation analysis in the family (pedigree shown in Figure 2(a)) confirmed mutations found in the patient (Figures 2(b) and 2(c)) and demonstrated that the mother is carrier of the c.3019C>G mutation, which is previously reported [6]. The father is carrier of the c.3259T>C mutation, which is a relatively common variant in European population [7] and was recently found in adult presentations of NPC disease [8]. The brother does not carry any of the mutations and is asymptomatic.


Clinical and genetic characteristics of mexican patients with juvenile presentation of niemann-pick type C disease.

Piña-Aguilar RE, Vera-Loaiza A, Chacón-Camacho OF, Zenteno JC, Nuñez-Orozco L, Santillán-Hernández Y - Case Rep Neurol Med (2014)

Families' pedigrees of Case 1 (a), Case 2 (d), and Case 3 (g), showing the mutations found. Partial DNA sequence of NPC1 gene of Case 1 showing the p.P1007A mutation in exon 20 (b) and p.F1087L mutation in exon 22 (c). Partial DNA sequence of NPC1 gene of Case 2 demonstrating p.Q921P mutation in exon 18 (e) and p.G992R mutation in exon 20 (f). Partial DNA sequence of NPC1 gene of Case 3 demonstrating p.R348∗ in exon 8 (h) and p.V1165M in exon 23 (i). NA: not available.
© Copyright Policy - open-access
Related In: Results  -  Collection

Show All Figures
getmorefigures.php?uid=PMC4202276&req=5

fig2: Families' pedigrees of Case 1 (a), Case 2 (d), and Case 3 (g), showing the mutations found. Partial DNA sequence of NPC1 gene of Case 1 showing the p.P1007A mutation in exon 20 (b) and p.F1087L mutation in exon 22 (c). Partial DNA sequence of NPC1 gene of Case 2 demonstrating p.Q921P mutation in exon 18 (e) and p.G992R mutation in exon 20 (f). Partial DNA sequence of NPC1 gene of Case 3 demonstrating p.R348∗ in exon 8 (h) and p.V1165M in exon 23 (i). NA: not available.
Mentions: Sequencing analysis showed heterozygous missense changes in NPC1, one in exon 20 c.3019C>G (p.P1007A) and the other in exon 22, c.3259T>C (p.F1087L). Neither mutations in NPC2 nor gross deletion/duplications in NPC1 or NPC2 were detected. Mutation analysis in the family (pedigree shown in Figure 2(a)) confirmed mutations found in the patient (Figures 2(b) and 2(c)) and demonstrated that the mother is carrier of the c.3019C>G mutation, which is previously reported [6]. The father is carrier of the c.3259T>C mutation, which is a relatively common variant in European population [7] and was recently found in adult presentations of NPC disease [8]. The brother does not carry any of the mutations and is asymptomatic.

Bottom Line: Mexican patients with juvenile NPC presented with a variable clinical phenotype and compound heterozygosity.This suggests a relative high frequency of mutation carriers as it is reported for European population.Consequently, clinicians should consider NPC as a diagnosis possibility in any adolescent or young adult patient with juvenile dementia and/or ataxia, even in absence of gelastic cataplexy and supranuclear vertical gaze palsy.

View Article: PubMed Central - PubMed

Affiliation: Department of Medical Genetics, Centro Médico Nacional "20 de Noviembre", ISSSTE, San Lorenzo No. 502E, Colonia del Valle Sur, Del. Benito Juárez, 03100 México, DF, Mexico.

ABSTRACT
Niemann-Pick type C disease (NPC) is a rare lysosomal disease with a protean presentation, ranging from a fatal neonatal course with visceromegaly to an adult presentation with only neurological or psychiatric symptomatology. In this report we describe the genetic and clinical characteristics of 3 Mexican patients from different families with juvenile presentation of NPC. Clinical examination, imaging of central nervous and gastrointestinal system, and EEG were performed. Genetic studies include sequencing and deletion/duplication analysis of NPC1 and NPC2 genes. All patients presented with cognitive impairment, ataxia, and supranuclear vertical gaze palsy; one case had gelastic cataplexy. Also they developed epilepsy and cortical atrophy and two patients had thinning of corpus callosum. The 3 patients were compound heterozygotes for NPC1 sequence variants, including 5 missense and 1 nonsense mutations: p.P1007A and p.F1087L in Case 1; p.Q921P and p.G992R in Case 2; and p.R348∗ and p.V1165M in case 3. Mexican patients with juvenile NPC presented with a variable clinical phenotype and compound heterozygosity. This suggests a relative high frequency of mutation carriers as it is reported for European population. Consequently, clinicians should consider NPC as a diagnosis possibility in any adolescent or young adult patient with juvenile dementia and/or ataxia, even in absence of gelastic cataplexy and supranuclear vertical gaze palsy.

No MeSH data available.


Related in: MedlinePlus