title: Duplication of exons 3-10 of the HSD17B3 gene: a novel type of genetic defect underlying 17β-HSD-3 deficiency.
abstract: 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.
authors.affiliation: Department of Molecular Genetics, Function and Therapy, The Cyprus Institute of Neurology and Genetics, 1683 Nicosia, Cyprus.
authors.forename: Vassos
authors.initials: V
authors.lastname: Neocleous
authors.forename: Carolina
authors.initials: C
authors.lastname: Sismani
authors.forename: Christos
authors.initials: C
authors.lastname: Shammas
authors.forename: Elisavet
authors.initials: E
authors.lastname: Efstathiou
authors.forename: Angelos
authors.initials: A
authors.lastname: Alexandrou
authors.forename: Marios
authors.initials: M
authors.lastname: Ioannides
authors.forename: Maria
authors.initials: M
authors.lastname: Argyrou
authors.forename: Philippos C
authors.initials: PC
authors.lastname: Patsalis
authors.forename: Leonidas A
authors.initials: LA
authors.lastname: Phylactou
authors.forename: Nicos
authors.initials: N
authors.lastname: Skordis
mesh_terms: D015067:17-Hydroxysteroid Dehydrogenases / Q000172:deficiency / Q000235:genetics*; D002648:Child; D004252:DNA Mutational Analysis; D012734:Disorders of Sex Development / Q000175:diagnosis / Q000235:genetics* / Q000473:pathology; D005091:Exons; D020440:Gene Duplication; D006801:Humans; D008297:Male; D020125:Mutation, Missense
chemical_list: D015067:17-Hydroxysteroid Dehydrogenases; C476565:17beta-hydroxysteroid dehydrogenase type 3