PERSONAL DE APOYO
MELITO Viviana Alicia
congresos y reuniones científicas
Título:
Genetic Analysis of Argentinean Variegate Population Patients
Autor/es:
GRANATA, B X; MELITO, V; BATLLE, A; PARERA, V; ROSSETTI, M.V
Lugar:
Lucerna
Reunión:
Congreso; INTERNATIONAL CONGRESS OF PORPHYRINS AND PORPHYRIAS; 2013
Resumen:
Variegate Porphyria (VP) is a disorder of heme biosynthesis that
results from a partial deficiency of Protoporphyrinogen Oxidase
(PPOX). It is essentially inherited as an autosomal dominant trait,
and can present acute, cutaneous or mixed symptoms. At present
about 150 different mutations in PPOX gene causing VP have been
reported.
The aim of this work is to give an overview of the molecular
studies conducted at the Centro de Investigaciones sobre Porfirinas
y Porfirias (CIPYP) in VP Argentinean patients.
Bereitgestellt von | De Gruyter / TCS
Angemeldet | 212.87.45.97
Heruntergeladen am | 08.05.13 10:31
Annual Assembly SSCC/Congress P&P, Lucerne, Switzerland, May 16?18, 2013 eA53eA53
So far, we have studied 35 unrelated Argentinean families at the
molecular level. All the mutations found are restrictive to one or at least
two families, except for c.1043insT which is present in 40 % of the families.
The majority of the mutations are exonic, except for c.338 + 3 insT
and c.808-1 G > C. These last two alterations proved to affect splicing,
as two other mutations present in the last (c.807G > A) and first
(c.808-1G > C) base of the corresponding exon. 10 % of the mutations
described in our country affect splicing. Among the exonic changes,
16 % are deletions and 40 % are insertions. All of them generate a
premature stop codon downstream. The 87,5 % of the insertions are
c.1043insT. The remaining 34 % of the mutations are missense, all of
them known to affect the enzymatic activity.
In terms of the symptoms, in the splicing group the main clinical
feature is the mixed one (45 % ). The deletions are mostly associated
with cutaneous symptoms (50 % ). The missense and all of the insertions
have a similar distribution pattern between the three types of
symptoms. Dividing the insertion group into c.1043insT and others,
the profile changes: while the most frequent insertion is associated to
a 30 % of cutaneous symptoms, the other insertions are 100 % linked
to acute signs; although the number of patients in this last group is
too small (four) to get a true conclusion about this.
In summary, we have a mutation that is strongly present in our
country (c.1043insT). Regarding the association with clinical features,
this mutation is not always accompanied by the same type
of symptom, which reveals that a genotype-phenotype relationship
cannot be established.
Nevertheless, it is important to scan the PPOX gene for this
alteration when a VP is suspected, since it is highly represented in
our population.
About the other mutations, the results are not sufficient to
ascertain a genotype-phenotype correlation.
described in our country affect splicing. Among the exonic changes,
16 % are deletions and 40 % are insertions. All of them generate a
premature stop codon downstream. The 87,5 % of the insertions are
c.1043insT. The remaining 34 % of the mutations are missense, all of
them known to affect the enzymatic activity.
In terms of the symptoms, in the splicing group the main clinical
feature is the mixed one (45 % ). The deletions are mostly associated
with cutaneous symptoms (50 % ). The missense and all of the insertions
have a similar distribution pattern between the three types of
symptoms. Dividing the insertion group into c.1043insT and others,
the profile changes: while the most frequent insertion is associated to
a 30 % of cutaneous symptoms, the other insertions are 100 % linked
to acute signs; although the number of patients in this last group is
too small (four) to get a true conclusion about this.
In summary, we have a mutation that is strongly present in our
country (c.1043insT). Regarding the association with clinical features,
this mutation is not always accompanied by the same type
of symptom, which reveals that a genotype-phenotype relationship
cannot be established.
Nevertheless, it is important to scan the PPOX gene for this
alteration when a VP is suspected, since it is highly represented in
our population.
About the other mutations, the results are not sufficient to
ascertain a genotype-phenotype correlation.
(c.808-1G > C) base of the corresponding exon. 10 % of the mutations
described in our country affect splicing. Among the exonic changes,
16 % are deletions and 40 % are insertions. All of them generate a
premature stop codon downstream. The 87,5 % of the insertions are
c.1043insT. The remaining 34 % of the mutations are missense, all of
them known to affect the enzymatic activity.
In terms of the symptoms, in the splicing group the main clinical
feature is the mixed one (45 % ). The deletions are mostly associated
with cutaneous symptoms (50 % ). The missense and all of the insertions
have a similar distribution pattern between the three types of
symptoms. Dividing the insertion group into c.1043insT and others,
the profile changes: while the most frequent insertion is associated to
a 30 % of cutaneous symptoms, the other insertions are 100 % linked
to acute signs; although the number of patients in this last group is
too small (four) to get a true conclusion about this.
In summary, we have a mutation that is strongly present in our
country (c.1043insT). Regarding the association with clinical features,
this mutation is not always accompanied by the same type
of symptom, which reveals that a genotype-phenotype relationship
cannot be established.
Nevertheless, it is important to scan the PPOX gene for this
alteration when a VP is suspected, since it is highly represented in
our population.
About the other mutations, the results are not sufficient to
ascertain a genotype-phenotype correlation.
described in our country affect splicing. Among the exonic changes,
16 % are deletions and 40 % are insertions. All of them generate a
premature stop codon downstream. The 87,5 % of the insertions are
c.1043insT. The remaining 34 % of the mutations are missense, all of
them known to affect the enzymatic activity.
In terms of the symptoms, in the splicing group the main clinical
feature is the mixed one (45 % ). The deletions are mostly associated
with cutaneous symptoms (50 % ). The missense and all of the insertions
have a similar distribution pattern between the three types of
symptoms. Dividing the insertion group into c.1043insT and others,
the profile changes: while the most frequent insertion is associated to
a 30 % of cutaneous symptoms, the other insertions are 100 % linked
to acute signs; although the number of patients in this last group is
too small (four) to get a true conclusion about this.
In summary, we have a mutation that is strongly present in our
country (c.1043insT). Regarding the association with clinical features,
this mutation is not always accompanied by the same type
of symptom, which reveals that a genotype-phenotype relationship
cannot be established.
Nevertheless, it is important to scan the PPOX gene for this
alteration when a VP is suspected, since it is highly represented in
our population.
About the other mutations, the results are not sufficient to
ascertain a genotype-phenotype correlation.
as two other mutations present in the last (c.807G > A) and first
(c.808-1G > C) base of the corresponding exon. 10 % of the mutations
described in our country affect splicing. Among the exonic changes,
16 % are deletions and 40 % are insertions. All of them generate a
premature stop codon downstream. The 87,5 % of the insertions are
c.1043insT. The remaining 34 % of the mutations are missense, all of
them known to affect the enzymatic activity.
In terms of the symptoms, in the splicing group the main clinical
feature is the mixed one (45 % ). The deletions are mostly associated
with cutaneous symptoms (50 % ). The missense and all of the insertions
have a similar distribution pattern between the three types of
symptoms. Dividing the insertion group into c.1043insT and others,
the profile changes: while the most frequent insertion is associated to
a 30 % of cutaneous symptoms, the other insertions are 100 % linked
to acute signs; although the number of patients in this last group is
too small (four) to get a true conclusion about this.
In summary, we have a mutation that is strongly present in our
country (c.1043insT). Regarding the association with clinical features,
this mutation is not always accompanied by the same type
of symptom, which reveals that a genotype-phenotype relationship
cannot be established.
Nevertheless, it is important to scan the PPOX gene for this
alteration when a VP is suspected, since it is highly represented in
our population.
About the other mutations, the results are not sufficient to
ascertain a genotype-phenotype correlation.
described in our country affect splicing. Among the exonic changes,
16 % are deletions and 40 % are insertions. All of them generate a
premature stop codon downstream. The 87,5 % of the insertions are
c.1043insT. The remaining 34 % of the mutations are missense, all of
them known to affect the enzymatic activity.
In terms of the symptoms, in the splicing group the main clinical
feature is the mixed one (45 % ). The deletions are mostly associated
with cutaneous symptoms (50 % ). The missense and all of the insertions
have a similar distribution pattern between the three types of
symptoms. Dividing the insertion group into c.1043insT and others,
the profile changes: while the most frequent insertion is associated to
a 30 % of cutaneous symptoms, the other insertions are 100 % linked
to acute signs; although the number of patients in this last group is
too small (four) to get a true conclusion about this.
In summary, we have a mutation that is strongly present in our
country (c.1043insT). Regarding the association with clinical features,
this mutation is not always accompanied by the same type
of symptom, which reveals that a genotype-phenotype relationship
cannot be established.
Nevertheless, it is important to scan the PPOX gene for this
alteration when a VP is suspected, since it is highly represented in
our population.
About the other mutations, the results are not sufficient to
ascertain a genotype-phenotype correlation.
(c.808-1G > C) base of the corresponding exon. 10 % of the mutations
described in our country affect splicing. Among the exonic changes,
16 % are deletions and 40 % are insertions. All of them generate a
premature stop codon downstream. The 87,5 % of the insertions are
c.1043insT. The remaining 34 % of the mutations are missense, all of
them known to affect the enzymatic activity.
In terms of the symptoms, in the splicing group the main clinical
feature is the mixed one (45 % ). The deletions are mostly associated
with cutaneous symptoms (50 % ). The missense and all of the insertions
have a similar distribution pattern between the three types of
symptoms. Dividing the insertion group into c.1043insT and others,
the profile changes: while the most frequent insertion is associated to
a 30 % of cutaneous symptoms, the other insertions are 100 % linked
to acute signs; although the number of patients in this last group is
too small (four) to get a true conclusion about this.
In summary, we have a mutation that is strongly present in our
country (c.1043insT). Regarding the association with clinical features,
this mutation is not always accompanied by the same type
of symptom, which reveals that a genotype-phenotype relationship
cannot be established.
Nevertheless, it is important to scan the PPOX gene for this
alteration when a VP is suspected, since it is highly represented in
our population.
About the other mutations, the results are not sufficient to
ascertain a genotype-phenotype correlation.
described in our country affect splicing. Among the exonic changes,
16 % are deletions and 40 % are insertions. All of them generate a
premature stop codon downstream. The 87,5 % of the insertions are
c.1043insT. The remaining 34 % of the mutations are missense, all of
them known to affect the enzymatic activity.
In terms of the symptoms, in the splicing group the main clinical
feature is the mixed one (45 % ). The deletions are mostly associated
with cutaneous symptoms (50 % ). The missense and all of the insertions
have a similar distribution pattern between the three types of
symptoms. Dividing the insertion group into c.1043insT and others,
the profile changes: while the most frequent insertion is associated to
a 30 % of cutaneous symptoms, the other insertions are 100 % linked
to acute signs; although the number of patients in this last group is
too small (four) to get a true conclusion about this.
In summary, we have a mutation that is strongly present in our
country (c.1043insT). Regarding the association with clinical features,
this mutation is not always accompanied by the same type
of symptom, which reveals that a genotype-phenotype relationship
cannot be established.
Nevertheless, it is important to scan the PPOX gene for this
alteration when a VP is suspected, since it is highly represented in
our population.
About the other mutations, the results are not sufficient to
ascertain a genotype-phenotype correlation.
> C. These last two alterations proved to affect splicing,
as two other mutations present in the last (c.807G > A) and first
(c.808-1G > C) base of the corresponding exon. 10 % of the mutations
described in our country affect splicing. Among the exonic changes,
16 % are deletions and 40 % are insertions. All of them generate a
premature stop codon downstream. The 87,5 % of the insertions are
c.1043insT. The remaining 34 % of the mutations are missense, all of
them known to affect the enzymatic activity.
In terms of the symptoms, in the splicing group the main clinical
feature is the mixed one (45 % ). The deletions are mostly associated
with cutaneous symptoms (50 % ). The missense and all of the insertions
have a similar distribution pattern between the three types of
symptoms. Dividing the insertion group into c.1043insT and others,
the profile changes: while the most frequent insertion is associated to
a 30 % of cutaneous symptoms, the other insertions are 100 % linked
to acute signs; although the number of patients in this last group is
too small (four) to get a true conclusion about this.
In summary, we have a mutation that is strongly present in our
country (c.1043insT). Regarding the association with clinical features,
this mutation is not always accompanied by the same type
of symptom, which reveals that a genotype-phenotype relationship
cannot be established.
Nevertheless, it is important to scan the PPOX gene for this
alteration when a VP is suspected, since it is highly represented in
our population.
About the other mutations, the results are not sufficient to
ascertain a genotype-phenotype correlation.
described in our country affect splicing. Among the exonic changes,
16 % are deletions and 40 % are insertions. All of them generate a
premature stop codon downstream. The 87,5 % of the insertions are
c.1043insT. The remaining 34 % of the mutations are missense, all of
them known to affect the enzymatic activity.
In terms of the symptoms, in the splicing group the main clinical
feature is the mixed one (45 % ). The deletions are mostly associated
with cutaneous symptoms (50 % ). The missense and all of the insertions
have a similar distribution pattern between the three types of
symptoms. Dividing the insertion group into c.1043insT and others,
the profile changes: while the most frequent insertion is associated to
a 30 % of cutaneous symptoms, the other insertions are 100 % linked
to acute signs; although the number of patients in this last group is
too small (four) to get a true conclusion about this.
In summary, we have a mutation that is strongly present in our
country (c.1043insT). Regarding the association with clinical features,
this mutation is not always accompanied by the same type
of symptom, which reveals that a genotype-phenotype relationship
cannot be established.
Nevertheless, it is important to scan the PPOX gene for this
alteration when a VP is suspected, since it is highly represented in
our population.
About the other mutations, the results are not sufficient to
ascertain a genotype-phenotype correlation.
(c.808-1G > C) base of the corresponding exon. 10 % of the mutations
described in our country affect splicing. Among the exonic changes,
16 % are deletions and 40 % are insertions. All of them generate a
premature stop codon downstream. The 87,5 % of the insertions are
c.1043insT. The remaining 34 % of the mutations are missense, all of
them known to affect the enzymatic activity.
In terms of the symptoms, in the splicing group the main clinical
feature is the mixed one (45 % ). The deletions are mostly associated
with cutaneous symptoms (50 % ). The missense and all of the insertions
have a similar distribution pattern between the three types of
symptoms. Dividing the insertion group into c.1043insT and others,
the profile changes: while the most frequent insertion is associated to
a 30 % of cutaneous symptoms, the other insertions are 100 % linked
to acute signs; although the number of patients in this last group is
too small (four) to get a true conclusion about this.
In summary, we have a mutation that is strongly present in our
country (c.1043insT). Regarding the association with clinical features,
this mutation is not always accompanied by the same type
of symptom, which reveals that a genotype-phenotype relationship
cannot be established.
Nevertheless, it is important to scan the PPOX gene for this
alteration when a VP is suspected, since it is highly represented in
our population.
About the other mutations, the results are not sufficient to
ascertain a genotype-phenotype correlation.
described in our country affect splicing. Among the exonic changes,
16 % are deletions and 40 % are insertions. All of them generate a
premature stop codon downstream. The 87,5 % of the insertions are
c.1043insT. The remaining 34 % of the mutations are missense, all of
them known to affect the enzymatic activity.
In terms of the symptoms, in the splicing group the main clinical
feature is the mixed one (45 % ). The deletions are mostly associated
with cutaneous symptoms (50 % ). The missense and all of the insertions
have a similar distribution pattern between the three types of
symptoms. Dividing the insertion group into c.1043insT and others,
the profile changes: while the most frequent insertion is associated to
a 30 % of cutaneous symptoms, the other insertions are 100 % linked
to acute signs; although the number of patients in this last group is
too small (four) to get a true conclusion about this.
In summary, we have a mutation that is strongly present in our
country (c.1043insT). Regarding the association with clinical features,
this mutation is not always accompanied by the same type
of symptom, which reveals that a genotype-phenotype relationship
cannot be established.
Nevertheless, it is important to scan the PPOX gene for this
alteration when a VP is suspected, since it is highly represented in
our population.
About the other mutations, the results are not sufficient to
ascertain a genotype-phenotype correlation.
> A) and first
(c.808-1G > C) base of the corresponding exon. 10 % of the mutations
described in our country affect splicing. Among the exonic changes,
16 % are deletions and 40 % are insertions. All of them generate a
premature stop codon downstream. The 87,5 % of the insertions are
c.1043insT. The remaining 34 % of the mutations are missense, all of
them known to affect the enzymatic activity.
In terms of the symptoms, in the splicing group the main clinical
feature is the mixed one (45 % ). The deletions are mostly associated
with cutaneous symptoms (50 % ). The missense and all of the insertions
have a similar distribution pattern between the three types of
symptoms. Dividing the insertion group into c.1043insT and others,
the profile changes: while the most frequent insertion is associated to
a 30 % of cutaneous symptoms, the other insertions are 100 % linked
to acute signs; although the number of patients in this last group is
too small (four) to get a true conclusion about this.
In summary, we have a mutation that is strongly present in our
country (c.1043insT). Regarding the association with clinical features,
this mutation is not always accompanied by the same type
of symptom, which reveals that a genotype-phenotype relationship
cannot be established.
Nevertheless, it is important to scan the PPOX gene for this
alteration when a VP is suspected, since it is highly represented in
our population.
About the other mutations, the results are not sufficient to
ascertain a genotype-phenotype correlation.
described in our country affect splicing. Among the exonic changes,
16 % are deletions and 40 % are insertions. All of them generate a
premature stop codon downstream. The 87,5 % of the insertions are
c.1043insT. The remaining 34 % of the mutations are missense, all of
them known to affect the enzymatic activity.
In terms of the symptoms, in the splicing group the main clinical
feature is the mixed one (45 % ). The deletions are mostly associated
with cutaneous symptoms (50 % ). The missense and all of the insertions
have a similar distribution pattern between the three types of
symptoms. Dividing the insertion group into c.1043insT and others,
the profile changes: while the most frequent insertion is associated to
a 30 % of cutaneous symptoms, the other insertions are 100 % linked
to acute signs; although the number of patients in this last group is
too small (four) to get a true conclusion about this.
In summary, we have a mutation that is strongly present in our
country (c.1043insT). Regarding the association with clinical features,
this mutation is not always accompanied by the same type
of symptom, which reveals that a genotype-phenotype relationship
cannot be established.
Nevertheless, it is important to scan the PPOX gene for this
alteration when a VP is suspected, since it is highly represented in
our population.
About the other mutations, the results are not sufficient to
ascertain a genotype-phenotype correlation.
> C) base of the corresponding exon. 10 % of the mutations
described in our country affect splicing. Among the exonic changes,
16 % are deletions and 40 % are insertions. All of them generate a
premature stop codon downstream. The 87,5 % of the insertions are
c.1043insT. The remaining 34 % of the mutations are missense, all of
them known to affect the enzymatic activity.
In terms of the symptoms, in the splicing group the main clinical
feature is the mixed one (45 % ). The deletions are mostly associated
with cutaneous symptoms (50 % ). The missense and all of the insertions
have a similar distribution pattern between the three types of
symptoms. Dividing the insertion group into c.1043insT and others,
the profile changes: while the most frequent insertion is associated to
a 30 % of cutaneous symptoms, the other insertions are 100 % linked
to acute signs; although the number of patients in this last group is
too small (four) to get a true conclusion about this.
In summary, we have a mutation that is strongly present in our
country (c.1043insT). Regarding the association with clinical features,
this mutation is not always accompanied by the same type
of symptom, which reveals that a genotype-phenotype relationship
cannot be established.
Nevertheless, it is important to scan the PPOX gene for this
alteration when a VP is suspected, since it is highly represented in
our population.
About the other mutations, the results are not sufficient to
ascertain a genotype-phenotype correlation.