A complex heterozygous mutation of His373Leu and Asp487–Ser488–Phe489 deletion in human cytochrome P450c17 causes 17α-hydroxylase/17,20-lyase deficiency in three Chinese sisters

Qiao, Jie; Hu, Renming; Peng, Yongde; Song, Hwangjun; Peng, Y.; Gao, Guofeng; Hao, Jian; Hu, Naibo; Xu, Man-yin; Chen, Jialun

doi:10.1016/s0303-7207(02)00156-9

Cited by 35 publications

(21 citation statements)

References 33 publications

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“…This mutation was first reported in a 14-yr-old Thai girl (16) and then detected in a Chinese patient from Hong Kong (17). We reported a compound heterozygous D487_F489del combined with H373L in three Chinese sisters (18). However, the position for nucleotide deletion in the present study was different from the previous report (1517_1525del vs. 1519_1527del), although the amino acid deletion was identical.…”

Section: Discussioncontrasting

confidence: 90%

Phenotype-Genotype Correlation in Eight Chinese 17α-Hydroxylase/17,20 Lyase-Deficiency Patients with Five Novel Mutations of CYP17A1 Gene

Yang

Cui

Sun

et al. 2006

The Journal of Clinical Endocrinology & Metabolism

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Section: Discussioncontrasting

confidence: 90%

Phenotype-Genotype Correlation in Eight Chinese 17α-Hydroxylase/17,20 Lyase-Deficiency Patients with Five Novel Mutations of CYP17A1 Gene

Yang

Cui

Sun

et al. 2006

The Journal of Clinical Endocrinology & Metabolism

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“…Almost 40 patients afflicted with 17OHD have been genotyped. The c.1517_1525del in exon 8 and the c.985_987delinsAA in exon 6 are reported to be the prevalent mutations of the CYP17A1 gene in China, nearly 90% of the patients bearing at least one of the mutations (11,(14)(15)(16)(17)(18). Both mutations were proved to completely abolish the CYP17A1 activity.…”

Section: Discussionmentioning

confidence: 99%

“…All eight exons of the CYP17A1 gene were amplified by PCR using eight pairs of primers, as described previously (11). The PCR products were purified by using a gel extraction kit (Qiagen) and sequenced in both the sense and the antisense directions on an ABI 3700 DNA sequencer (Applied Biosystems PerkinElmer, Foster City, CA, USA).…”

Section: Cyp17a1 Gene Analysismentioning

confidence: 99%

A unique exonic splicing mutation in the CYP17A1 gene as the cause for steroid 17α-hydroxylase deficiency

Qiao¹,

Han²,

Liu³

et al. 2011

European Journal of Endocrinology

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Background: 17a-Hydroxylase/17,20-lyase deficiency (17OHD) caused by a mutation in the CYP17A1 gene is characterized by hypertension, hypokalemia, and abnormal development of the genitalia. The majority of CYP17A1 mutations are located in the coding sequence, and several intronic splicing site mutations have been reported. Objective: A 2.5-year-old girl with 46,XY disordered sex development exhibited a nearly normal basal cortisol level and reduced sexual steroids. This study is aimed to explore the molecular basis and analyze its possible influence on the phenotype of the patient. Methods and results: Mutation analysis revealed compound heterozygous CYP17A1 mutations, with c.985_987delinsAA in one allele and a synonymous substitution (c.1263GOA) in another allele. In vitro expression analysis of the allelic minigene showed that the novel nucleotide variation located in exon 8 induces a splicing signal, which results in an aberrant splicing of CYP17A1 mRNA and a missing portion of exon 8. The translation product includes the deletion of six or seven amino acids from residue position 415 without causing a frameshift. Consistent with the result of molecular modeling, functional studies in transiently transfected HEK-293T cells with the aberrantly spliced enzyme proteins showed that the deleted proteins completely abolished the enzyme activity. However, RT-PCR indicated the existence of a small fraction of normal, functionally intact enzyme, which may explain the partial masculinization of this patient. Conclusion: This is the first description of an exonic splicing mutation in CYP17A1 relevant to the 17OHD phenotype. It also demonstrates the importance of studying synonymous change in such patients with less severe phenotype.

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“…Reports of CYP17 gene mutations are uncommon among patients with CAH in Asian populations studied, including Japanese, Korean, Chinese, and Thai patients [7][8][9][10][11][12][13]. We report here a Han Chinese in Taiwan with 17a-hydroxylase/ 17,20-lyase deficiency carrying a compound heterozygous mutation in the CYP17 gene.…”

Section: Introductionmentioning

confidence: 88%

A compound heterozygous mutation in the CYP17 (17α-hydroxylase/17,20-lyase) gene in a Chinese subject with congenital adrenal hyperplasia

Won¹,

Chiu

Tso

et al. 2007

Metabolism

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A complex heterozygous mutation of His373Leu and Asp487–Ser488–Phe489 deletion in human cytochrome P450c17 causes 17α-hydroxylase/17,20-lyase deficiency in three Chinese sisters

Cited by 35 publications

References 33 publications

Phenotype-Genotype Correlation in Eight Chinese 17α-Hydroxylase/17,20 Lyase-Deficiency Patients with Five Novel Mutations of CYP17A1 Gene

Phenotype-Genotype Correlation in Eight Chinese 17α-Hydroxylase/17,20 Lyase-Deficiency Patients with Five Novel Mutations of CYP17A1 Gene

A unique exonic splicing mutation in the CYP17A1 gene as the cause for steroid 17α-hydroxylase deficiency

A compound heterozygous mutation in the CYP17 (17α-hydroxylase/17,20-lyase) gene in a Chinese subject with congenital adrenal hyperplasia

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