TY - JOUR
T1 - Duplication of exons 3-10 of the HSD17B3 gene
T2 - A novel type of genetic defect underlying 17β-HSD-3 deficiency
AU - Neocleous, Vassos
AU - Sismani, Carolina
AU - Shammas, Christos
AU - Efstathiou, Elisavet
AU - Alexandrou, Angelos
AU - Ioannides, Marios
AU - Argyrou, Maria
AU - Patsalis, Philippos C.
AU - Phylactou, Leonidas A.
AU - Skordis, Nicos
PY - 2012/5/15
Y1 - 2012/5/15
N2 - The clinical, biochemical and genetic features of a Cypriot origin male of non-consanguineous parents due to 17β-hydroxysteroid dehydrogenase type 3 (17β-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 Müllerian structures identified on pelvic ultrasound. Chromosomal analysis showed an apparently normal male 46,XY karyotype. Diagnosis of 17β-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 17β-HSD-3. In conclusion, 17β-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 17β-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.
AB - The clinical, biochemical and genetic features of a Cypriot origin male of non-consanguineous parents due to 17β-hydroxysteroid dehydrogenase type 3 (17β-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 Müllerian structures identified on pelvic ultrasound. Chromosomal analysis showed an apparently normal male 46,XY karyotype. Diagnosis of 17β-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 17β-HSD-3. In conclusion, 17β-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 17β-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.
KW - 17β-HSD-3
KW - Androstenedione (δ4)
KW - Disorder of Sex Development (DSD)
KW - HSD17B3 gene
KW - Testosterone (T)
UR - http://www.scopus.com/inward/record.url?scp=84860228416&partnerID=8YFLogxK
U2 - 10.1016/j.gene.2012.03.031
DO - 10.1016/j.gene.2012.03.031
M3 - Article
C2 - 22445608
AN - SCOPUS:84860228416
SN - 0378-1119
VL - 499
SP - 250
EP - 255
JO - Gene
JF - Gene
IS - 2
ER -