A cluster of progranulin C157KfsX97 mutations in Southern Italy: clinical characterization and genetic correlations.
Frontotemporal lobar degeneration (FTLD) is a group of neurodegenerative diseases displaying high clinical, pathologic, and genetic heterogeneity. Several autosomal dominant progranulin (GRN) mutations have been reported, accounting for 5%-10% of FTLD cases worldwide. In this study, we described the clinical characteristics of 7 Italian patients, 5 with a diagnosis of frontotemporal dementia behavioral variant and 2 of corticobasal syndrome (CBS), carrying the GRN deletion g.101349_101355delCTGCTGT, resulting in the C157KfsX97 null mutation, and hypothesized the existence of a founder effect by means of haplotype sharing analysis. We performed plasma progranulin dosage, GRN gene sequencing, and haplotype sharing study, analyzing 10 short tandem repeat markers, spanning a region of 11.08 Mb flanking GRN on chromosome 17q21. We observed shared alleles among 6 patients for 8 consecutive short tandem repeat markers spanning a 7.29 Mb region. Therefore, also with this particular mutation, the elevated clinical variability described among GRN-mutated FTLD cases is confirmed. Moreover, this is the first study reporting the likely existence of a founder effect for C157KfsX97 mutation in Southern Italy.
Second Division of Neurology, Department of Medical, Surgical, Neurological, Metabolic and Aging Sciences, Second University of Naples, Naples, Italy. Electronic address: cinzia.coppola@unina2.it.
Cinzia
C
Coppola
Second Division of Neurology, Department of Medical, Surgical, Neurological, Metabolic and Aging Sciences, Second University of Naples, Naples, Italy.
Dario
D
Saracino
Second Division of Neurology, Department of Medical, Surgical, Neurological, Metabolic and Aging Sciences, Second University of Naples, Naples, Italy.
Gianfranco
G
Puoti
Second Division of Neurology, Department of Medical, Surgical, Neurological, Metabolic and Aging Sciences, Second University of Naples, Naples, Italy.
Giacomo
G
Lus
Second Division of Neurology, Department of Medical, Surgical, Neurological, Metabolic and Aging Sciences, Second University of Naples, Naples, Italy.
Clemente
C
Dato
Institut du Cerveau et de la Moelle épinière (ICM), INSERM U1127, CNRS UMR 7225, Sorbonne Universités, Université Pierre et Marie Curie, Univ Paris 06, UPMC-P6 UMR S 1127 Hôpital de la Pitié-Salpêtrière, Paris, France; AP-HP, Hôpital de la Pitié-Salpêtrière, Centre de Référence des Démences Rares & Fédération des maladies du système nerveux, Paris, France.
Isabelle
I
Le Ber
Service de neurologie, CHU Toulouse, Toulouse, France.
Jeremie
J
Pariente
Division of Neurology V-Neuropathology, Fondazione IRCCS Istituto Neurologico Carlo Besta, Milan, Italy.
Paola
P
Caroppo
Division of Neurology V-Neuropathology, Fondazione IRCCS Istituto Neurologico Carlo Besta, Milan, Italy.
Elena
E
Piccoli
Division of Neurology V-Neuropathology, Fondazione IRCCS Istituto Neurologico Carlo Besta, Milan, Italy.
Fabrizio
F
Tagliavini
Second Division of Neurology, Department of Medical, Surgical, Neurological, Metabolic and Aging Sciences, Second University of Naples, Naples, Italy.
Giuseppe
G
Di Iorio
Division of Neurology V-Neuropathology, Fondazione IRCCS Istituto Neurologico Carlo Besta, Milan, Italy.
Giacomina
G
Rossi
D000368:Aged; D000483:Alleles; D005260:Female; D018703:Founder Effect; D057174:Frontotemporal Lobar Degeneration / Q000235:genetics*; D017353:Gene Deletion; D018628:Gene Dosage; D005799:Genes, Dominant / Q000235:genetics; D056726:Genetic Association Studies; D006239:Haplotypes; D006801:Humans; D036341:Intercellular Signaling Peptides and Proteins / Q000097:blood / Q000235:genetics*; D007558:Italy; D008297:Male; D008875:Middle Aged; D005810:Multigene Family / Q000235:genetics*; D009154:Mutation / Q000235:genetics*; D000077153:Progranulins; D017422:Sequence Analysis, DNA; D020080:Tandem Repeat Sequences
C492314:GRN protein, human; D036341:Intercellular Signaling Peptides and Proteins; D000077153:Progranulins
Corticobasal syndrome; Founder effect; Frontotemporal lobar degeneration; GRN; Mutation; Progranulin protein