Abstract
X-linked sideroblastic anemia (XLSA) is caused by mutations in the erythroid-specific 5-aminolevulinic acid synthase (ALAS2) gene. Hemizygous males have microcytic anemia and iron overload. A 38-year-old male presented with this phenotype (hemoglobin [Hb] 7.6 g/dL, mean corpuscular volume [MCV] 64 fL, serum ferritin 859 μg/L), and molecular analysis of ALAS2 showed a mutation 1731G>A predicting an Arg560His amino acid change. A 36-year-old brother was hemizygous for this mutation and expressed the mutated ALAS2 mRNA in his reticulocytes, but showed almost no phenotypic expression. All 5 heterozygous females from this family, including the 3 daughters of the nonanemic hemizygous male, showed marginally increased red-cell distribution width (RDW). Although variable penetrance for XLSA in males has been previously described, this is the first report showing that phenotypic expression can be absent in hemizygous males. This observation is relevant to genetic counseling, emphasizing the importance of gene-based diagnosis.
| Original language | English |
|---|---|
| Pages (from-to) | 4236-4238 |
| Number of pages | 3 |
| Journal | Blood |
| Volume | 100 |
| Issue number | 12 |
| DOIs | |
| Publication status | Published - Dec 1 2002 |
Fingerprint
ASJC Scopus subject areas
- Hematology
Cite this
Absent phenotypic expression of X-linked sideroblastic anemia in one of 2 brothers with a novel ALAS2 mutation. / Cazzola, Mario; May, Alison; Bergamaschi, Gaetano; Cerani, Paola; Ferrillo, Sara; Bishop, David F.
In: Blood, Vol. 100, No. 12, 01.12.2002, p. 4236-4238.Research output: Contribution to journal › Article
}
TY - JOUR
T1 - Absent phenotypic expression of X-linked sideroblastic anemia in one of 2 brothers with a novel ALAS2 mutation
AU - Cazzola, Mario
AU - May, Alison
AU - Bergamaschi, Gaetano
AU - Cerani, Paola
AU - Ferrillo, Sara
AU - Bishop, David F.
PY - 2002/12/1
Y1 - 2002/12/1
N2 - X-linked sideroblastic anemia (XLSA) is caused by mutations in the erythroid-specific 5-aminolevulinic acid synthase (ALAS2) gene. Hemizygous males have microcytic anemia and iron overload. A 38-year-old male presented with this phenotype (hemoglobin [Hb] 7.6 g/dL, mean corpuscular volume [MCV] 64 fL, serum ferritin 859 μg/L), and molecular analysis of ALAS2 showed a mutation 1731G>A predicting an Arg560His amino acid change. A 36-year-old brother was hemizygous for this mutation and expressed the mutated ALAS2 mRNA in his reticulocytes, but showed almost no phenotypic expression. All 5 heterozygous females from this family, including the 3 daughters of the nonanemic hemizygous male, showed marginally increased red-cell distribution width (RDW). Although variable penetrance for XLSA in males has been previously described, this is the first report showing that phenotypic expression can be absent in hemizygous males. This observation is relevant to genetic counseling, emphasizing the importance of gene-based diagnosis.
AB - X-linked sideroblastic anemia (XLSA) is caused by mutations in the erythroid-specific 5-aminolevulinic acid synthase (ALAS2) gene. Hemizygous males have microcytic anemia and iron overload. A 38-year-old male presented with this phenotype (hemoglobin [Hb] 7.6 g/dL, mean corpuscular volume [MCV] 64 fL, serum ferritin 859 μg/L), and molecular analysis of ALAS2 showed a mutation 1731G>A predicting an Arg560His amino acid change. A 36-year-old brother was hemizygous for this mutation and expressed the mutated ALAS2 mRNA in his reticulocytes, but showed almost no phenotypic expression. All 5 heterozygous females from this family, including the 3 daughters of the nonanemic hemizygous male, showed marginally increased red-cell distribution width (RDW). Although variable penetrance for XLSA in males has been previously described, this is the first report showing that phenotypic expression can be absent in hemizygous males. This observation is relevant to genetic counseling, emphasizing the importance of gene-based diagnosis.
UR - http://www.scopus.com/inward/record.url?scp=0036893199&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=0036893199&partnerID=8YFLogxK
U2 - 10.1182/blood-2002-03-0685
DO - 10.1182/blood-2002-03-0685
M3 - Article
C2 - 12393718
AN - SCOPUS:0036893199
VL - 100
SP - 4236
EP - 4238
JO - Blood
JF - Blood
SN - 0006-4971
IS - 12
ER -