Duplication of exons 3-10 of the HSD17B3 gene: A novel type of genetic defect underlying 17尾-HSD-3 deficiency

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• 作者：Vassos Neocleous^a ; Carolina Sismani^b ; Christos Shammas^a ; Elisavet Efstathiou^c ; Angelos Alexandrou^b ; Marios Ioannides^b ; Maria Argyrou^c ; Philippos C. Patsalis^b ; Leonidas A. Phylactou^a ; Nicos Skordis^c ; ^a ; ^d ; ^{nskordis@cytanet.com.cy}
• 关键词：17尾-HSD-3 ; 17尾-hydroxysteroid dehydrogenase type 3 deficiency ; hCG ; human chorionic gonadotrophin ; MLPA ; Multiplex Ligation Probe Amplification ; PCR ; Polymerase chain reaction
• 刊名：Gene
• 出版年：2012
• 期刊代码：73_03781119
• 类别：bio
• 出版时间：15 May, 2012
• 卷：499
• 期：2
• 页码：250-255
• 文件大小：1142 K

摘要

The clinical, biochemical and genetic features of a Cypriot origin male of non-consanguineous parents due to 17尾-hydroxysteroid dehydrogenase type 3 (17尾-HSD-3) deficiency are presented. The patient, currently a 10 old male, was referred to our clinic because of ambiguous genitalia at birth. Gonads were palpable in the inguinal canal bilaterally and no M眉llerian structures identified on pelvic ultrasound. Chromosomal analysis showed an apparently normal male 46,XY karyotype. Diagnosis of 17尾-HSD-3 deficiency in the newborn was suspected based on biochemical findings, following human chorionic gonadotrophin (hCG) stimulation test. Sequence analysis and real time PCR along with MLPA identified the patient with a novel 11.96 kb duplication that spans exons 3-10 of the HSD17B3 gene and extends from intron 2 to intron 10 in compound heterozygosity with the known p.R80Q missense mutation leading to 17尾-HSD-3. In conclusion, 17尾-HSD-3 deficiency was diagnosed in this patient based on endocrinologic evaluation and confirmed with genetic analysis of the HSD17B3 gene. The novel large duplication spanning exons 3-10 of the HSD17B3 gene that we report here in compound heterozygosity with the known p.R80Q leads to 17尾-HSD-3 deficiency presenting as 46,XY Disorder of Sex Development. Following diagnosis and appropriate genetic counselling, the patient was raised a boy and successfully underwent surgical correction of crytptorchidism and hypospadias.