[Gene mutation analyses in Chinese children with multiple carboxylase deficiency].
OBJECTIVE
To confirm the diagnosis of multiple carboxylase deficiency (MCD) on the gene level and explore the mutations in Chinese children with MCD.


METHODS
Biotinidase (BT) and holocarboxylase synthetase (HLCS) genes were analyzed by PCR and direct sequencing for the 4 BT deficiency patients and 8 HLCS deficiency patients, respectively. The identified mutations in the parents of the patients and 50 normal controls were screened by PCR-restriction fragment length polymorphism and direct DNA sequencing.


RESULTS
Total detection rate of gene mutation is 100% in the 12 children with MCD. Six mutations were detected in the 4 children with BT deficiency, they were c. 98-104del7ins3, c. 1369G>A (V457M), c. 1157G>A(W386X), c. 1284C>A(Y428X), c. 1384delA and c. 1493_1494insT. The last four were novel mutations. Four mutations were found in the 8 children with HLCS deficiency. They were c. 126G>T (E42D), c. 1994G>C (R665P), c. 1088T>A (V363D) and c. 1522C>T (R508W). The last two were hot-spot mutations [75%(12/16)], and c. 1994G>C (R665P) was a novel mutation.


CONCLUSIONS
This study confirmed the diagnosis of 12 patients with MCD on the gene level. Six mutations were found in the BT gene and 4 in the HLCS gene, including 5 novel mutations. Two mutations of the HLCS gene are probably hot-spot mutations in Chinese children with HLCS deficiency.
Wang
Tong
T
Department of Pediatric Endocrinology and Genetic Metabolism, Xinhua Hospital Affiliated to Shanghai Jiaotong University School of Medicine, PR China.
Ye
Jun
J
Han
Lian-shu
LS
Qiu
Wen-juan
WJ
Zhang
Hui-wen
HW
Zhang
Ya-fen
YF
Gao
Xiao-lan
XL
Wang
Yu
Y
Gu
Xue-fan
XF
D044466:Asian People / Q000235:genetics*; D001483:Base Sequence; D043523:Biotinidase / Q000235:genetics*; D028921:Biotinidase Deficiency; D019731:Carbon-Nitrogen Ligases / Q000172:deficiency / Q000235:genetics*; D016022:Case-Control Studies; D002648:Child; D002675:Child, Preschool; D005260:Female; D006801:Humans; D007223:Infant; D008297:Male; D008969:Molecular Sequence Data; D009100:Multiple Carboxylase Deficiency / Q000235:genetics* / Q000378:metabolism; D009154:Mutation
D043523:Biotinidase; D019731:Carbon-Nitrogen Ligases; C023312:holocarboxylase synthetases