TY - JOUR
T1 - Autosomal-dominant Alport syndrome
T2 - Natural history of a disease due to COL4A3 or COL4A4 gene
AU - Pescucci, Chiara
AU - Mari, Francesca
AU - Longo, Ilaria
AU - Vogiatzi, Paraskevi
AU - Caselli, Rossella
AU - Scala, Elisa
AU - Abaterusso, Cataldo
AU - Gusmano, Rosanna
AU - Seri, Marco
AU - Miglietti, Nunzia
AU - Bresin, Elena
AU - Renieri, Alessandra
PY - 2004/5
Y1 - 2004/5
N2 - Background. Alport syndrome is a clinically and genetically heterogeneous nephropathy. The majority of cases are transmitted as an X-linked semidominant condition due to COL4A5 mutations. In this form males are more severely affected than females. Less than 10% of cases are autosomal recessive due to mutation in either COL4A3 or COL4A4. In this rarer form, both males and females are severely affected. Only two cases of autosomal-dominant Alport syndrome have been reported, one due to a COL4A3 mutation and the other due to a COL4A4 mutation. Because of the paucity of the reported families, the natural history of autosomal-dominant Alport syndrome is mostly unknown. Methods. Four families with likely autosomal-dominant Alport syndrome were investigated. COL4A3 and COL4A4 genes were analyzed by denaturing high-performance liquid chromatography (HPLC). Automated sequencing was performed to identify the underlying mutation. Results. Two families had a mutation in the COL4A4 gene and two in the COL4A3. Accurate clinical evaluation of family members showed interesting results. Affected individuals (22 persons) had a wide range of phenotypes from end-stage renal disease (ESRD) in the fifth decade to a nonprogressive isolated microhematuria. Finally, three heterozygous individuals (90, 22 and 11 years old, respectively) were completely asymptomatic. Conclusion. This paper demonstrated that patients affected by autosomal-dominant Alport syndrome have a high clinical variability. Moreover, a reduced penetrance of about 90% (3 of 25) may be considered for the assessment of recurrence risk during genetic counseling of these families.
AB - Background. Alport syndrome is a clinically and genetically heterogeneous nephropathy. The majority of cases are transmitted as an X-linked semidominant condition due to COL4A5 mutations. In this form males are more severely affected than females. Less than 10% of cases are autosomal recessive due to mutation in either COL4A3 or COL4A4. In this rarer form, both males and females are severely affected. Only two cases of autosomal-dominant Alport syndrome have been reported, one due to a COL4A3 mutation and the other due to a COL4A4 mutation. Because of the paucity of the reported families, the natural history of autosomal-dominant Alport syndrome is mostly unknown. Methods. Four families with likely autosomal-dominant Alport syndrome were investigated. COL4A3 and COL4A4 genes were analyzed by denaturing high-performance liquid chromatography (HPLC). Automated sequencing was performed to identify the underlying mutation. Results. Two families had a mutation in the COL4A4 gene and two in the COL4A3. Accurate clinical evaluation of family members showed interesting results. Affected individuals (22 persons) had a wide range of phenotypes from end-stage renal disease (ESRD) in the fifth decade to a nonprogressive isolated microhematuria. Finally, three heterozygous individuals (90, 22 and 11 years old, respectively) were completely asymptomatic. Conclusion. This paper demonstrated that patients affected by autosomal-dominant Alport syndrome have a high clinical variability. Moreover, a reduced penetrance of about 90% (3 of 25) may be considered for the assessment of recurrence risk during genetic counseling of these families.
KW - Autosomal-dominant Alport syndrome
KW - Collagen IV genes
KW - Incomplete penetrance
KW - Inherited nephropathy
KW - Phenotypic variability
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U2 - 10.1111/j.1523-1755.2004.00560.x
DO - 10.1111/j.1523-1755.2004.00560.x
M3 - Article
C2 - 15086897
AN - SCOPUS:2342647451
VL - 65
SP - 1598
EP - 1603
JO - Kidney International
JF - Kidney International
SN - 0085-2538
IS - 5
ER -