TY - JOUR

T1 - Single-nucleotide variations in the genes encoding the mitochondrial Hsp60/Hsp10 chaperone system and their disease-causing potential

AU - Bross, Peter

AU - Li, Zhijie

AU - Hansen, Jakob

AU - Hansen, Jens Jacob

AU - Nielsen, Marit Nyholm

AU - Corydon, Thomas Juhl

AU - Georgopoulos, Costa

AU - Ang, Debbie

AU - Lundemose, Jytte Banner

AU - Niezen-Koning, Klary

AU - Eiberg, Hans Rudolf Lytchoff

AU - Yang, Huanming

AU - Kølvraa, Steen

AU - Bolund, Lars

AU - Gregersen, Niels

PY - 2007

Y1 - 2007

N2 - Molecular chaperones assist protein folding, and variations in their encoding genes may be disease-causing in themselves or influence the phenotypic expression of disease-associated or susceptibility-conferring variations in many different genes. We have screened three candidate patient groups for variations in the HSPD1 and HSPE1 genes encoding the mitochondrial Hsp60/Hsp10 chaperone complex: two patients with multiple mitochondrial enzyme deficiency, 61 sudden infant death syndrome cases (MIM: #272120), and 60 patients presenting with ethylmalonic aciduria carrying non-synonymous susceptibility variations in the ACADS gene (MIM: *606885 and #201470). Besides previously reported variations we detected six novel variations: two in the bidirectional promoter region, and one synonymous and three non-synonymous variations in the HSPD1 coding region. One of the non-synonymous variations was polymorphic in patient and control samples, and the rare variations were each only found in single patients and absent in 100 control chromosomes. Functional investigation of the effects of the variations in the promoter region and the non-synonymous variations in the coding region indicated that none of them had a significant impact. Taken together, our data argue against the notion that the chaperonin genes play a major role in the investigated diseases. However, the described variations may represent genetic modifiers with subtle effects.

AB - Molecular chaperones assist protein folding, and variations in their encoding genes may be disease-causing in themselves or influence the phenotypic expression of disease-associated or susceptibility-conferring variations in many different genes. We have screened three candidate patient groups for variations in the HSPD1 and HSPE1 genes encoding the mitochondrial Hsp60/Hsp10 chaperone complex: two patients with multiple mitochondrial enzyme deficiency, 61 sudden infant death syndrome cases (MIM: #272120), and 60 patients presenting with ethylmalonic aciduria carrying non-synonymous susceptibility variations in the ACADS gene (MIM: *606885 and #201470). Besides previously reported variations we detected six novel variations: two in the bidirectional promoter region, and one synonymous and three non-synonymous variations in the HSPD1 coding region. One of the non-synonymous variations was polymorphic in patient and control samples, and the rare variations were each only found in single patients and absent in 100 control chromosomes. Functional investigation of the effects of the variations in the promoter region and the non-synonymous variations in the coding region indicated that none of them had a significant impact. Taken together, our data argue against the notion that the chaperonin genes play a major role in the investigated diseases. However, the described variations may represent genetic modifiers with subtle effects.

KW - Butyryl-CoA Dehydrogenase

KW - Chaperonin 10

KW - Chaperonin 60

KW - Child

KW - Child, Preschool

KW - Genetic Predisposition to Disease

KW - Humans

KW - Infant

KW - Infant, Newborn

KW - Malonates

KW - Mitochondrial Proteins

KW - Polymorphism, Single Nucleotide

KW - Promoter Regions, Genetic

KW - Sudden Infant Death

U2 - 10.1007/s10038-006-0080-7

DO - 10.1007/s10038-006-0080-7

M3 - Journal article

C2 - 17072495

VL - 52

SP - 56

EP - 65

JO - Journal of Human Genetics

JF - Journal of Human Genetics

SN - 1434-5161

IS - 1

ER -