Molecular Genetics of Niemann-Pick Type C Disease in Italy: An Update on 105 Patients and Description of 18 NPC1 Novel Variants

被引:23
作者
Dardis, Andrea [1 ]
Zampieri, Stefania [1 ]
Gellera, Cinzia [2 ]
Carrozzo, Rosalba [3 ]
Cattarossi, Silvia [1 ]
Peruzzo, Paolo [1 ]
Dariol, Rosalia [1 ]
Sechi, Annalisa [1 ]
Deodato, Federica [4 ]
Caccia, Claudio [2 ]
Verrigni, Daniela [3 ]
Gasperini, Serena [5 ]
Fiumara, Agata [6 ]
Fecarotta, Simona [7 ]
Carecchio, Miryam [2 ,8 ]
Filosto, Massimiliano [9 ]
Santoro, Lucia [10 ]
Borroni, Barbara [11 ]
Bordugo, Andrea [12 ,13 ]
Brancati, Francesco [14 ]
Russo, Cinzia V. [15 ]
Di Rocco, Maja [16 ]
Toscano, Antonio [17 ]
Scarpa, Maurizio [1 ]
Bembi, Bruno [1 ]
机构
[1] Univ Hosp Udine, Reg Coordinator Ctr Rare Dis, I-33100 Udine, Italy
[2] Fdn IRCCS Ist Neurol Carlo Besta, Unit Genet Neurodegenerat & Metab Dis, I-20133 Milan, Italy
[3] Bambino Gesu Pediat Hosp, IRCCS, Lab Mol Med, Unit Muscular & Neurodegenerat Disorders, I-00146 Rome, Italy
[4] Bambino Gesu Pediat Hosp, IRCCS, Div Metab, Dept Pediat Subspecial, I-00146 Rome, Italy
[5] MBBM Fdn, ATS Monza & Brianza, Dept Pediat, Pediat Rare Dis Unit, I-20900 Monza, Italy
[6] Univ Catania, Reg Referral Ctr Inherited Metab Dis, Dept Pediat, I-95123 Catania, Italy
[7] Federico II Univ Hosp, Dept Pediat, I-80131 Naples, Italy
[8] Univ Padua, Dept Neurosci, Via Giustiniani 2, I-35128 Padua, Italy
[9] ASST Spedali Civili & Univ Brescia, Unit Neurol, Ctr Neuromuscular Dis, I-25123 Brescia, Italy
[10] Polytech Univ Marche, Ospedali Riuniti, Div Pediat, Dept Clin Sci, I-60020 Ancona, Italy
[11] Univ Brescia, Dept Clin & Expt Sci, Ctr Neurodegenerat Disorders, I-25123 Brescia, Italy
[12] Azienda Osped Univ Integrata, Children & Women Hosp, Inherited Metab Dis Unit, I-37126 Verona, Italy
[13] Azienda Osped Univ Integrata, Children & Women Hosp, Reg Ctr Newborn Screening, I-37126 Verona, Italy
[14] Tor Vergata Univ, Med Genet Unit, I-00133 Rome, Italy
[15] Univ Naples Federico II, Dept Neurosci Reprod & Odontostomatol Sci, I-80138 Naples, Italy
[16] Giannina Gaslini Inst, Unit Rare Dis, Dept Pediat, I-16147 Genoa, Italy
[17] Univ Messina, Dept Neurosci, I-98125 Messina, Italy
关键词
Niemann-Pick C disease; NPC1; NPC2; mutations; STEROL-SENSING DOMAIN; MUTATION NOMENCLATURE; PROTEIN; NIEMANN-PICK-C1-DISEASE; IDENTIFICATION; SCHIZOPHRENIA; INVOLVEMENT; IMPROVEMENT; EXPRESSION; PHENOTYPE;
D O I
10.3390/jcm9030679
中图分类号
R5 [内科学];
学科分类号
1002 ; 100201 ;
摘要
Niemann-Pick type C (NPC) disease is an autosomal recessive lysosomal storage disorder caused by mutations in NPC1 or NPC2 genes. In 2009, the molecular characterization of 44 NPC Italian patients has been published. Here, we present an update of the genetic findings in 105 Italian NPC patients belonging to 83 unrelated families (77 NPC1 and 6 NPC2). NPC1 and NPC2 genes were studied following an algorithm recently published. Eighty-four different NPC1 and five NPC2 alleles were identified. Only two NPC1 alleles remained non detected. Sixty-two percent of NPC1 alleles were due to missense variants. The most frequent NPC1 mutation was the p.F284Lfs*26 (5.8% of the alleles). All NPC2 mutations were found in the homozygous state, and all but one was severe. Among newly diagnosed patients, 18 novel NPC1 mutations were identified. The pathogenic nature of 7/9 missense alleles and 3/4 intronic variants was confirmed by filipin staining and NPC1 protein analysis or mRNA expression in patient's fibroblasts. Taken together, our previous published data and new results provide an overall picture of the molecular characteristics of NPC patients diagnosed so far in Italy.
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页数:21
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