Deficiency of the a subunit of succinate-coenzyme A ligase causes fatal infantile lactic acidosis with mitochondrial DNA depletion

被引：133

作者：

Ostergaard, Elsebet

Christensen, Ernst

Kristensen, Elisabeth

Mogensen, Bodil

Duno, Morten

Shoubridge, Eric A.

Wibrand, Flemming

机构：

[1] Natl Univ Hosp, Rigshosp, Dept Clin Genet 4062, DK-2100 Copenhagen, Denmark

[2] Natl Univ Hosp, Rigshosp, Dept Pathol, DK-2100 Copenhagen, Denmark

[3] Kennedy Inst, Natl Eye Clin, Glostrup, Denmark

[4] McGill Univ, Dept Human Genet, Montreal, PQ H3A 2T5, Canada

[5] McGill Univ, Montreal Neurol Inst, Montreal, PQ H3A 2T5, Canada

来源：

AMERICAN JOURNAL OF HUMAN GENETICS | 2007年 / 81卷 / 02期

关键词：

D O I：

10.1086/519222

中图分类号：

Q3 [遗传学];

学科分类号：

071007 ; 090102 ;

摘要：

Fatal infantile lactic acidosis is a severe metabolic disorder characterized by the onset of lactic acidosis within the 1st d of life and early death. We found a combined respiratory-chain enzyme deficiency associated with mitochondrial DNA (mtDNA) depletion in a small consanguineous family with this disorder. To identify the disease-causing gene, we performed single-nucleotide polymorphism homozygosity mapping and found homozygous regions on four chromosomes. DNA sequencing revealed a homozygous 2-bp deletion in SUCLG1, a gene that encodes the a subunit of the Krebs-cycle enzyme succinate-coenzyme A ligase (SUCL). The mtDNA depletion is likely explained by decreased mitochondrial nucleoside diphosphate kinase (NDPK) activity resulting from the inability of NDPK to form a complex with SUCL.

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页码：383 / 387

页数：5

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