close

Вход

Забыли?

вход по аккаунту

?

000059882

код для вставкиСкачать
Sessa A, Conte F, Meroni M, Battini G (eds): Hereditary Kidney Diseases.
Contrib Nephrol. Basel, Karger, 1997, vol 122, pp 132–133
...........................
Molecular Diagnosis of Alport
Syndrome: The Experience in Siena
Alessandra Renieri a, Mirella Bruttini a, Monica Piccini a, Michele Bruno b,
Milvia Cecconi c, Maura Conti d, Rosanna Coppo e,Angela La Manna f,
Antonella Trivelli g, Mario De Marchi h, Andrea Ballabio a
a
GeneticMedicine, Department of Molecular Biology, University of Siena,
Department of Nephrology, General Hospital of Turin,
c
Department of Clinical Pediatrics, General Hospital of Ancona,
d
Department of Nephrology, General Hospital of Cagliari,
e
Department of Clinical Pediatrics, General Hospital of Turin,
f
Department of Clinical Pediatrics, General Hospital of Naples,
g
Department of Nephrology, General Hospital of Genoa, and
h
Department of Clinical and Biological Science, General Hospital of Turin, Italy
b
Downloaded by:
Université René Descartes Paris 5
193.51.85.197 - 10/27/2017 9:07:23 AM
We previously reported an extensive molecular characterization of patients
affected by Alport syndrome (AS) [1] (1996). After this analysis which concerned 201 families, another 230 DNA samples belonging to 57 families were
referred to the Medical Genetics Unit of Siena with a request for molecular
diagnosis for AS.
For technical reasons, analysis was done set by set, each set containing
at least 16 samples. Analysis of the first two sets (32 families) is complete.
Among these cases, only 19 had either electron microscopic lesions or classical
clinical criteria of AS. Among these 19, twelve had a clear X-linked inheritance,
3 were sporadic and 4 were autosomal recessive cases.
COL4A3/COL4A4 screening families were selected by formal genetics
and linkage analysis. Four cases were compatible with a mutation in the
COL4A3/COL4A4 genes. A cell line from the proband of each 4 families was
established. SSCP screening at the mRNA level is ongoing.
COL4A5 gene screening proband’s DNA from each family underwent
SSCP screening of 51 exons COL4A5 gene. In the first 32 patients we have
found 8 mutations including three glycine substitutions in the triple helical
domain, a cystein for serine substitution in the NC domain, one frame-shift
Table 1.
Name
Nucleotide
change
Effect on
coding sequence
Predicted effect on
protein
Exon Family
GKA at 1287
GKT at 2358
GKT at 3603
CKG at 4665
GlyKGlu at 362
GlyKVal at 719
GlyKVal at 1134
SerKCys at 1488
interrupts GLy-X-Y
interrupts Gly-X-Y
interrupts Gly-X-Y
additional cystein
19
28
38
47
MIN
LAV
ANT
BRO
insertion of C
after 1573
frame-shift
chain termination
21
LNZ
In frame insertion
1907dup145 dupl. of 45 bp dupl. 15 amino acid chain elongation
24
BAA
Splicing
1625 GKA
21
PIS
Missense
G362E
G719V
G1134V
S1488C
Frame-shift
1573insC
GKA at 1625
5€ splice signal
skips exon 21
Rearrangements 3€ deletion
NTR
insertion, one frame duplication, one splice site mutation and one major
rearrangement (table 1).
A mutation in the COL4A5 gene was found in one third of sporadic cases
and seven twelfths of X-linked cases with either electron microscopy lesions
or classical clinical criteria of AS. Thus, as previously defined [1], a mutation
was found in about an half of the cases with X-linked AS.
Reference
Renieri A, Bruttini M, Galli L, Zanelli P, Neri T, Rossetti S, Turco A, Heiskari N, Zhou J, Gusmano
R, Massella L, Banfi G, Scolari F, Sessa A, Rizzoni G, Tryggvason K, Pignatti PF, Savi M, Ballabio
A, DeMarchi M: X-linked Alport syndrome: An SSCP-based mutation survey over all 51 exons of
the COL4A5 gene. Am J Hum Genet 1996;58:1192–1204.
Alessandra Renieri,MD, Genetica Medica Dip Biol Mol Università di Siena,
Viale Bracci, I–53100 Siena (Italy)
Molecular Diagnosis of Alport Syndrome: The Experience in Siena
133
Downloaded by:
Université René Descartes Paris 5
193.51.85.197 - 10/27/2017 9:07:23 AM
1
Документ
Категория
Без категории
Просмотров
0
Размер файла
123 Кб
Теги
000059882
1/--страниц
Пожаловаться на содержимое документа