Gene mutations and prenatal diagnosis in families with maple syrup urine disease

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Author:
YANG Nan(Department of Pediatric Endocrinology, Genetic and Metabolic Disease, Shanghai Institute of Pediatric Research, Xinhua Hospital, Shanghai Jiaotong University School of Medicine, Shanghai 200092, China)
GU Xue-fan(Department of Pediatric Endocrinology, Genetic and Metabolic Disease, Shanghai Institute of Pediatric Research, Xinhua Hospital, Shanghai Jiaotong University School of Medicine, Shanghai 200092, China)
ZHANG Li-qin(Maternal and Children Health Care Center of Qingdao , Qingdao 266011 , China)
HAN Lian-shu(Department of Pediatric Endocrinology, Genetic and Metabolic Disease, Shanghai Institute of Pediatric Research, Xinhua Hospital, Shanghai Jiaotong University School of Medicine, Shanghai 200092, China)
YE Jun(Department of Pediatric Endocrinology, Genetic and Metabolic Disease, Shanghai Institute of Pediatric Research, Xinhua Hospital, Shanghai Jiaotong University School of Medicine, Shanghai 200092, China)
QIU Wen-juan(Department of Pediatric Endocrinology, Genetic and Metabolic Disease, Shanghai Institute of Pediatric Research, Xinhua Hospital, Shanghai Jiaotong University School of Medicine, Shanghai 200092, China)
ZHANG Hui-wen(Department of Pediatric Endocrinology, Genetic and Metabolic Disease, Shanghai Institute of Pediatric Research, Xinhua Hospital, Shanghai Jiaotong University School of Medicine, Shanghai 200092, China)
GONG Zhu-wen(Department of Pediatric Endocrinology, Genetic and Metabolic Disease, Shanghai Institute of Pediatric Research, Xinhua Hospital, Shanghai Jiaotong University School of Medicine, Shanghai 200092, China)
ZHANG Ya-fen(Department of Pediatric Endocrinology, Genetic and Metabolic Disease, Shanghai Institute of Pediatric Research, Xinhua Hospital, Shanghai Jiaotong University School of Medicine, Shanghai 200092, China)
ZHU Jian-xing()
Journal Title:
Chinese Journal of Perinatal Medicine
Issue:
Volume 15, Issue 08, 2012
DOI:
10.3760/cma.j.issn.1007-9408.2012.08.013
Key Word:
Maple syrup urine disease;3-Methyl-2-oxobutanoate dehydrogenase (lipoamide);Pedigree;Prenatal diagnosis

Abstract: Objective Maple syrup urine disease (MSUD) is a rare metabolic disorder caused by deficiency of the activity of branched-chain 2-keto acid dehydrogenase complex.The complex contains E1α,E1β and E2 subunits which are encoded by BCKDHA,BCKDHB or DBT genes respectively.Mutation in any gene will cause MSUD.The aim of this study was to analyze the gene mutations of four cases with MSUD and carry out prenatal diagnosis for these four families for MSUD.Methods From 2005 to 2010,four neonates (two males and two females) were diagnosed as MSUD at 2,5,10and 26 days of life.The coding regions of BCKDHA gene and BCKDHB gene in the above four cases were amplified by polymerase chain reaction and analyzed by direct DNA sequencing.During the second pregnancy of the same mother,the amniotic fluid was drawn out at 16-20 weeks for gene mutation analysis after the amniocytes were cultured.Results Mutation analysis revealed six mutations in four patients,including four novel mutations (c.308T>C,c.562G>T,c.1279C>G and c.1280-1291de112) and two previously reported mutations.Five mutations (c.308T>C,c.562G >T,c.868G>A,c.1279C>G and c.1280-1291de112) were detected on BCKDHA gene in three patients.While one mutation (c.853C>T) was found on BCKDHB gene in one patient.Only one mutation was found in the amniocytes of each patient's mother at their second pregnancies suggesting a MSUD heterozygous fetus.Conclusions Analysis of BCKDHA and BCKDHB allowed preliminary understand of gene mutations in the four MSUD families,and made prenatal diagnosis possible,which helped in consultation in the second pregnancy.

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