PMID- 10408532
OWN - NLM
STAT- MEDLINE
DCOM- 19990809
LR  - 20190514
IS  - 0028-3878 (Print)
IS  - 0028-3878 (Linking)
VI  - 53
IP  - 1
DP  - 1999 Jul 13
TI  - Genetic heterogeneity in Italian families with familial hemiplegic migraine.
PG  - 26-33
AB  - OBJECTIVE: To verify linkage to chromosome 19p13, to detect mutations in the
      CACNA1A gene, and to correlate genetic results to their clinical phenotypes in
      Italian families with familial hemiplegic migraine (FHM). BACKGROUND: FHM is an
      autosomal dominant disease, classified as a subtype of migraine with aura. Only a
      proportion of FHM patients have been associated with chromosome 19p13. Among
      these, four missense mutations within the CACNA1A gene in five unrelated families
      have been described. METHODS: A linkage study was performed in 19 patients
      affected by FHM from five families by studying microsatellite markers associated 
      with the 19p13 region. All familial and seven additional sporadic patients with
      FHM were analyzed to search for mutations within the CACNA1A gene by applying the
      double gradient-denaturant gradient electrophoresis technique. RESULTS: Lod score
      values did not establish significantly linkage to chromosome 19. However, seven
      new genetic variants were detected: six were new polymorphisms. The seventh was a
      missense mutation present in family 1, and it was associated with a hemiplegic
      migraine phenotype without unconsciousness and cerebellar ataxia. Because this
      missense mutation is absent in the general population and cosegregates with the
      disease, it may be a pathologic mutation. CONCLUSIONS: Genetic heterogeneity of
      FHM has been shown in familial and sporadic FHM patients of Italian origin. The
      new missense mutation-G4644T-is associated with milder clinical features compared
      with typical FHM.
FAU - Carrera, P
AU  - Carrera P
AD  - IRCCS H San Raffaele, Laboratorio Biologia Molecolare Clinica, Italy.
      carrera.paola@hsr.it
FAU - Piatti, M
AU  - Piatti M
FAU - Stenirri, S
AU  - Stenirri S
FAU - Grimaldi, L M
AU  - Grimaldi LM
FAU - Marchioni, E
AU  - Marchioni E
FAU - Curcio, M
AU  - Curcio M
FAU - Righetti, P G
AU  - Righetti PG
FAU - Ferrari, M
AU  - Ferrari M
FAU - Gelfi, C
AU  - Gelfi C
LA  - eng
PT  - Case Reports
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
PL  - United States
TA  - Neurology
JT  - Neurology
JID - 0401060
RN  - 0 (CACNA1A protein, human)
RN  - 0 (Cacna1a protein, rat)
RN  - 0 (Calcium Channels)
RN  - 0 (Genetic Markers)
RN  - 9007-49-2 (DNA)
SB  - IM
CIN - Neurology. 1999 Jul 13;53(1):3-4. PMID: 10408526
MH  - Adolescent
MH  - Adult
MH  - Amino Acid Sequence
MH  - Amino Acid Substitution
MH  - Animals
MH  - Calcium Channels/*genetics
MH  - Cerebellar Ataxia
MH  - Child
MH  - Chromosome Mapping
MH  - *Chromosomes, Human, Pair 19
MH  - DNA/blood
MH  - Exons
MH  - Female
MH  - Genetic Linkage
MH  - Genetic Markers
MH  - Hemiplegia/*genetics
MH  - Humans
MH  - Introns
MH  - Male
MH  - Microsatellite Repeats
MH  - Middle Aged
MH  - Migraine Disorders/*genetics
MH  - Molecular Sequence Data
MH  - Mutagenesis, Site-Directed
MH  - *Mutation, Missense
MH  - Pedigree
MH  - Polymerase Chain Reaction
MH  - Rabbits
MH  - Rats
MH  - Sequence Alignment
EDAT- 1999/07/17 00:00
MHDA- 1999/07/17 00:01
CRDT- 1999/07/17 00:00
PHST- 1999/07/17 00:00 [pubmed]
PHST- 1999/07/17 00:01 [medline]
PHST- 1999/07/17 00:00 [entrez]
AID - 10.1212/wnl.53.1.26 [doi]
PST - ppublish
SO  - Neurology. 1999 Jul 13;53(1):26-33. doi: 10.1212/wnl.53.1.26.