TY - JOUR
T1 - Frequency of heterozygous Parkin mutations in healthy subjects: Need for careful prospective follow-up examination of mutation carriers
AU - Brüggemann, Norbert
AU - Mitterer, Manfred
AU - Lanthaler, Andrea J.
AU - Djarmati, Ana
AU - Hagenah, Johann
AU - Wiegers, Karin
AU - Winkler, Susen
AU - Pawlack, Heike
AU - Lohnau, Thora
AU - Pramstaller, Peter P.
AU - Klein, Christine
AU - Lohmann, Katja
PY - 2009/7/1
Y1 - 2009/7/1
N2 - The role of single heterozygous mutations in the putatively recessive Parkin gene in Parkinson disease (PD) is a vividly debated issue, partly caused by the largely unknown frequency of these mutations in healthy individuals. We investigated mutations in all 12 Parkin exons in 356 controls from two European populations including individuals from South Tyrol and Germany. None of the controls carried a homozygous or compound heterozygous mutation. Seventeen carriers of rare heterozygous alterations were detected, of which 13 (13/356; 3.7%) are considered to alter protein structure including four different gene dosage alterations, four missense mutations, and two frameshift mutations. Two of the mutations occurred recurrently in the South Tyrolean population. There was no obvious difference in the mutation frequency between the two populations. One of the presumably healthy mutation carrier was available for re-examination at the age of 67 years. He presented with mild signs of parkinsonism but not fulfilling diagnostic criteria for definite PD. To elucidate the role of heterozygosity is important for genetic testing and counseling of mutation carriers. A detailed clinical prospective and follow-up examination of mutation carriers is required for a better understanding of the role of heterozygous Parkin mutations.
AB - The role of single heterozygous mutations in the putatively recessive Parkin gene in Parkinson disease (PD) is a vividly debated issue, partly caused by the largely unknown frequency of these mutations in healthy individuals. We investigated mutations in all 12 Parkin exons in 356 controls from two European populations including individuals from South Tyrol and Germany. None of the controls carried a homozygous or compound heterozygous mutation. Seventeen carriers of rare heterozygous alterations were detected, of which 13 (13/356; 3.7%) are considered to alter protein structure including four different gene dosage alterations, four missense mutations, and two frameshift mutations. Two of the mutations occurred recurrently in the South Tyrolean population. There was no obvious difference in the mutation frequency between the two populations. One of the presumably healthy mutation carrier was available for re-examination at the age of 67 years. He presented with mild signs of parkinsonism but not fulfilling diagnostic criteria for definite PD. To elucidate the role of heterozygosity is important for genetic testing and counseling of mutation carriers. A detailed clinical prospective and follow-up examination of mutation carriers is required for a better understanding of the role of heterozygous Parkin mutations.
UR - http://www.scopus.com/inward/record.url?scp=67549146854&partnerID=8YFLogxK
U2 - 10.1016/j.parkreldis.2008.11.014
DO - 10.1016/j.parkreldis.2008.11.014
M3 - Journal articles
C2 - 19162522
AN - SCOPUS:67549146854
SN - 1353-8020
VL - 15
SP - 425
EP - 429
JO - Parkinsonism and Related Disorders
JF - Parkinsonism and Related Disorders
IS - 6
ER -