All-dielectric geometric metasurfaces for the generation and manipulation of perfect high-order Poincaré sphere beams.

A high-order Poincaré sphere (HOPS) can be used to describe high-order modes of waveguides and vector beams, since it generalizes the feature of spin and the orbital angular momentum of light. HOPS beams are such beams with polarization states on the HOPS, which have potential applications in optical manipulation and optical communication. In general, the intensity distribution of this kind of beam changes with the topological charge, which limits their practical applications. Based on the concept of perfect vortex beams (PVBs), perfect HOPS beams have been proposed to solve this problem. Here, a flexible and compact scheme based on all-dielectric metasurfaces for realizing and manipulating perfect HOPS beams at near-infrared wavelength was demonstrated. Geometric-phase-only manipulation was employed for simultaneously controlling the phase and polarization of the incident light. By varying the incident polarization, several selected polarization states on the HOPS could be realized by the proposed metasurface. Further, the single ultra-thin metasurface can also realize high quality multiplexing perfect HOPS beams that carry different topological charges. Finally, a cascaded metasurface system has been proposed for generating and manipulating multiple HOPS beams. This compact flat-optics-based scheme for perfect HOPS beam generation and manipulation demonstrated here can be used for on-chip optical manipulation and integrated optical communication in the future.

Super-resolution imaging based on radially polarized beam induced superoscillation using an all-dielectric metasurface.

Superoscillation is a kind of phenomenon which can generate oscillation faster than the fastest component of a band-limited function. For optics, superoscillation is generated by coherence of low spatial frequency waves. It can bring a localized region named "hot spot", which has a smaller size than the diffraction-limit, and this character has potential applicaions in super-resolution imaging. Using a high-order radially polarized Laguerre-Gaussian beam tightly focused by high-NA objective lens, we can easily obtain and control the superoscillation hot spot. Using a metasurface, which has compact volume and sub-wavelength pixel size, we can generate the high-order radially polarized Laguerre-Gaussian beam more simply than conventional methods like using a liquid crystal mode converter. We first analyze the properties of unit cells of the metasurface and simulate the performance of the metasurface. Then we analyze the property of the tightly focused high-order radially polarized Laguerre-Gaussian beam and design a super-resolution imaging system using our designed metasurface. Therefore, the 2-fold lateral resolution enhancement is realized in our approach. This method can be used to improve lateral resolution in conventional confocal imaging systems.

High-performance terahertz vortex beam generator based on square-split-ring metasurfaces.

Generating a vortex beam is a fundamental task due to the potential applications in wireless communication. Here we propose a kind of high-performance terahertz vortex beam generator with several topological numbers based on the square-split-ring metasurfaces. Via the Fabry-Perot resonance effect of the structure, the transmittance of an orthogonal polarization mode could be remarkably enhanced. We use a Laguerre-Gaussian (LG) mode for illustration and then simulate the far-field propagation of the LG beam by using phase superposition of focusing lens and vortex phase plates. The theoretical and simulation results agree well, which implies a bright application prospect.

Next-generation sequencing reveals genetic landscape in 46, XY disorders of sexual development patients with variable phenotypes.

Disorders of sexual development (DSD) are rare congenital conditions in which chromosomal, gonadal, or anatomical sex is atypical. Currently, less than 20% of patients receive an accurate genetic diagnosis. Targeted next-generation sequencing, consisting of 33 candidate genes and 47 genes involved in sexual differentiation and development, was performed on 70 46, XY DSD patients. Functional assays were performed to evaluate the expression and transcriptional activity of one reported and nine novel mutations of NR5A1. In total, 113 mutations, including 86 novel and 27 reported sites in 40 genes, were identified in 52 patients. Among them, 37 mutations from 19 genes were first identified in 46, XY DSD patients, including EGF, LHX9, and CST9. Nine patients displayed biallelic mutations, 12 had mutations in sex chromosome genes and 14 had monoallelic mutations in NR5A1, BMP4, and WT1. Higher frequency mutations were identified in AR, SRD5A2, and NR5A1. Six missense, one frameshift, and one three-nucleotide deletion mutations of NR5A1 were shown to impair the transactivation ability with an altered nuclear aggregation of p.T29K and p.N44del variants. Multiple genetic mutations were identified in 33 of the 70 patients. The targeted sequencing panel provides an efficient method for the etiological diagnosis of 46, XY DSD patients and expands the candidate genes and inherited patterns.

Bone morphogenetic protein 7-transduced human dermal-derived fibroblast cells differentiate into osteoblasts and form bone in vivo.

BACKGROUND: Human dermal-derived fibroblast cells (hDDFCs) are multipotent. Bone morphogenetic proteins (BMPs) are a group of cytokines that promote different developmental processes, including the formation of bone. BMPs can promote hDDFC osteogenesis, but the role of BMP7 in hDDFC osteogenesis in vitro and bone formation in vivo has not been investigated in depth. MATERIALS AND METHODS: hDDFCs were stably transfected with a human BMP7 recombinant adenovirus and osteogenic differentiation was examined by alkaline phosphatase staining and calcium accumulation. In addition, we measured the expression of osteoblast-related genes. To examine osteogenesis in vivo, we injected C57BL/6 nude mice with adenovirus-transfected hDDFCs in a calcium alginate hydrogel and examined bone formation using soft X-ray, histological, and immunohistochemical analyses. RESULTS: Our findings showed that adenovirus-mediated BMP7 expression promoted osteogenic differentiation of hDDFCs and enhanced expression of osteoblast-related genes in vitro. Cells infected with BMP7 adenoviruses showed enhanced bone formation and osteoblast-related gene expression in vivo after the injection of hDDFC-hydrogel mixture. CONCLUSIONS: Taken together, our data indicate that BMP7 significantly promotes hDDFC osteogenesis, and confirm that infecting hDDFCs with BMP7-expressing adenoviruses is a useful tool for bone tissue engineering.

Incidence and Features of Vertebral Fractures After Scalp Avulsion Injuries.

BACKGROUND: Scalp injuries are usually extensive and may have a deleterious impact for the patient. To date, little is known in the literature about simultaneous vertebral fractures. The aim of this study was to analyze the frequency, features and pathogenesis of vertebrae fractures after scalp avulsion injuries. METHODS: Between 2004 and 2014, 64 patients were retrospectively identified after scalp avulsion injuries. Patient records were reviewed for mechanism of trauma, clinical examination and neurological deficits. The features of vertebral fractures were evaluated by X-ray, computed tomography or magnetic resonance imaging, where necessary. Various treatment options were evaluated according to their injuries. RESULTS: Totally, 6 women (9.4%) with a mean age 37 ± 6 years were identified with cervical fractures due to scalp avulsion injuries (mean size defect 808 ± 56 cm). Clinical examination revealed neurological deficits in 3 patients. Five patients were diagnosed with different types of C2 fracture and 1 patient was diagnosed with C7 fracture. One patient had simultaneous fractures of T3/T4. Treatment for the scalp avulsion consisted in either composite graft in 5 patients or microsurgical replantation in 1 patient. The vertebral fractures were treated by collar protection (3), cervical traction (1), HALO fixation (1), and internal stabilization (1), respectively. CONCLUSIONS: Most vertebral fractures associated with scalp avulsion injuries are C2 fractures. Careful and appropriate examination is mandatory for patients with scalp avulsion injuries to exclude vertebral fractures which, if not recognized early, can have serious and devastating consequences.

Phenotypic and molecular characteristics in eleven Chinese patients with 5α-reductase Type 2 deficiency.

CONTEXT: Steroid 5α-reductase type 2 deficiency (5α-RD2) is a male-limited, autosomal recessive inherited disease. Affected 46, XY individuals usually present with ambiguous genitalia at birth. An early and precise diagnosis is of great value to the long-term prognosis of the disease. OBJECTIVE: To describe the clinical features and molecular determinants in 11 Chinese patients with the SRD5A2 gene mutation and to investigate the functional alteration arising from a novel splicing site mutation identified in one of the patients. SUBJECTS AND METHODS: Eleven subjects born with abnormal external genitalia from 10 unrelated families were recruited. Among them, nine patients who were reared as girls underwent virilization and gender change after puberty. Genotyping analysis of the SRD5A2 gene was performed in each of the patients. Haplotype analysis was performed in five patients with a prevalent mutation of p.G203S to illustrate the founder effect in China. Functional impairment of the new variant was explored by an in vitro splicing study and enzymatic activity assay. RESULTS: Nine mutations in the SRD5A2 gene were detected in the eleven patients. In addition to the previously reported p.G203S, p.R227Q, p.N193S, p.R246Q, p.Q6X, p.A228V, c.655delT and IVS1-2 A>G, a novel splicing site mutation (IVS4 + 2 T>C) was identified. From an in vitro functional study, this mutation was found to result in a skipping of exon 4 in the course of mRNA splicing, leading to a truncated protein of 205 amino acids that lacks the catalysing activity. Two siblings with the same compound heterozygous mutation (IVS1-2A>G/p.G203S) exhibited differing phenotypes and opposite patterns of gender rearing. A prevalent variation p.V89L combined with c.655delT was revealed to cause a mild phenotype of 5α-RD2 with a micropenis. CONCLUSION: This cohort study describes the phenotypic, biochemical and long-term outcome in 11 Chinese patients with 5α-RD2 deficiency and defines the genotypic spectrum of SRD5A2 mutations in China.

A new surgical procedure for phallic reconstruction in partial penis necrosis: penile elongation in combination with glanuloplasty.

The radial forearm flap transfer has proved to be the standard technique in penile reconstruction. However, this operation still leads to a residual scar on the forearm. In the reconstruction of partial penis necrosis, achieving a desirable appearance and functional recovery while minimizing donor-site damage remains an unsolved problem. In this study, we report our experience using penile elongation combined with glanuloplasty to rebuild the partially necrotic penis.A retrospective review of a consecutive series of 33 patients with partial penis necrosis after microwave thermotherapy (not from our hospital) from December 2008 to May 2012 was conducted at the Department of Plastic and Reconstructive Surgery, Shanghai 9th People's Hospital. These patients, with an age range from 20 to 36 years, first underwent a scrotal skin flap transfer to cover residual cavernosum. The penis was simultaneously elongated at the proximal end. Six months later, all patients received glanuloplasty using expanded polytetrafluoroethylene that was implanted at the distal end of transferred scrotal skin flap to create the neoglans.Anthropometric measurements of preoperative and postoperative penile length were performed with an average follow-up period of 28 months. The mean extended penile length average was 2.57 cm, ranging from 3.16 to 5.73 cm. Patients' satisfaction rate was 88%. In addition, preoperative and postoperative photographs were reviewed for objective and subjective assessment of outcome parameters such as appearance of neophallus, urination, and erogenous sensation. Most importantly, the rebuilt penis postoperatively showed almost normal shape and restoration of basic physiologic function in most of the patients, with an acceptable complication rate. These preliminary results may provide a useful strategy for the reconstruction of a partially necrotic penis using a novel, simple, and effective approach.

Fasciocutaneous foreskin twin flaps in hypospadias repair: Reconstructing a functional penis with freestyle design.

BACKGROUND: Hypospadias is the most common congenital urological deformity in males; however, there is still no perfect solution or surgical method for one-stage operations to fix proximal hypospadias with ventral penile curvature (VPC). We developed a fasciocutaneous foreskin twin flap technique that can provide freestyle flap designs in hypospadias repair. METHODS: A retrospective study including 26 patients was performed between January 2017 and June 2020. The surgical procedures included VPC correction, skin flap design, transfer and reconstruction. The urethra and shaft were reconstructed by twin flaps in one stage. All patients were followed up until 12 months. RESULTS: All VPC cases were corrected after the operation. The fistula rate was 11.5% (3/26). No meatal stenosis, urethral diverticulum, or stricture was observed. A total of 92.3% (24/26) of patients were satisfied with their penis appearance. CONCLUSIONS: The fasciocutaneous foreskin twin flaps provide freestyle designs in hypospadias repair, which can achieve a one-stage operation for proximal hypospadias with low fistula rates.

Autologous rib cartilage as implanted stiffener of phalloplasty: comparing three different methods.

BACKGROUND: Maintaining the length, rigidity, and appearance of a reconstructed phallus in the long term has been challenging for phalloplasty and may depend on choosing the optimal implanted stiffener. The aim of this study was to determine the best type of stiffener for a reconstructed phallus regarding aesthetic and functional parameters. METHODS: From 1987 to 2018, 376 individuals underwent phalloplasty at a single institution of which 81 met the following inclusion criteria: biological male gender, age between 18 and 60 years, radial forearm flap for tube-within-a-tube phalloplasty with rib cartilage and secondary glans sculpting and unimpaired urination preoperatively. Those were divided into three groups with regard to different types of autologous rib cartilage stiffener. A group with a cartilage strip, T-shaped cartilage, and mushroom-shaped cartilage group were evaluated regarding preserved length and aesthetic features of the phallus during a minimum period of 12 months. The rib cartilage length in the phallus was 10.5 cm in all groups. RESULTS: The length of the phallus was 10.8 ± 0.5 cm in the cartilage strip group, 11.3 ± 0.3 cm in the T-shaped cartilage group and 11.3 ± 0.3 cm in the mushroom-shaped cartilage group at 1-year postoperatively. The aesthetic appearance score of mushroom-shaped cartilage group was 1.67 ± 0.48, significantly higher than the cartilage strip group (1.38 ± 0.50, p = 0.03) at 1 year after surgery. CONCLUSIONS: The mushroom-shaped autologous rib cartilage group showed superior length preservation and aesthetic appearance and appeared as the best type of stiffener for one-phase phalloplasty.

The strategy for vaginal rejuvenation: CO2 laser or vaginoplasty?

BACKGROUND: Vaginal laxity may result from trauma to the pelvic floor muscle, which may affect patients' sensation and quality of life. Vaginal rejuvenation, including surgical or nonsurgical interventions, aims to improve laxity. In this study, we aimed to establish a strategy for vaginal rejuvenation by comparing surgical and nonsurgical methods. METHODS: A retrospective clinical study was performed on patients who complained about vaginal laxity from 2017 to 2019. The degree of vaginal laxity severity was evaluated by vaginal examination in each patient. The patients were categorized as having a light, moderate or severe degree of vaginal laxity, and different correction methods were chosen accordingly. The Female Sexual Function Index (FSFI) questionnaire was administered to the patients preoperatively and at three months and one year after treatment. RESULTS: Seventeen patients with severe-degree vaginal laxity were treated with vaginoplasty. The total FSFI score was 23.21±2.57 before the operation and significantly increased to 29.36±1.84 (P<0.01) at one year after surgery. Eleven patients with moderate-degree vaginal laxity were treated with vaginoplasty and had a significant improvement in the total FSFI score at one year after surgery (29.86±1.74, P<0.01) compared with the FSFI score before surgery (23.41±2.84). Three patients with moderate-degree vaginal laxity were treated with a CO2 laser and tended to have increased FSFI scores but did not show significant improvement after the operation. CO2 laser treatment was performed on 16 patients with light-degree vaginal laxity. The total FSFI score improved from 23.76±2.35 to 26.16±2.58 at one year (P<0.05). CONCLUSIONS: The strategy for vaginal rejuvenation should be selected based on the degree of vaginal laxity severity. Surgical treatment is suitable for severe- and moderate-degree vaginal laxity while nonsurgical treatment is suitable for light-degree vaginal laxity.

A splice site mutation combined with a novel missense mutation of LHCGR cause male pseudohermaphroditism.

Leydig cell hypoplasia (LCH) is a rare form of male pseudohermaphroditism caused by inactivating mutations in the luteinizing hormone receptor gene (LHCGR). The majority of LHCGR mutations are located in the coding sequence, resulting in impairment of either LH/CG binding or signal transduction. We report a Chinese family with two siblings (46, XY and 46, XX) carrying a missense mutation (c. 455 T>C, p. Ile152Thr) and a splice site mutation (c. 537-3 C>A). Computational analysis of the missense mutation in the three-dimensional structural model predicted it might influence the distribution of hydrogen bonds and intermolecular contacts between the hormone and receptor. Consistent with these findings, in vitro mutant analysis revealed a marked impairment of human chorionic gonadotropin binding and signal transduction. The splice-acceptor mutation (c. 537-3 C>A) resulted in abnormal splicing of LHCGR mRNA, skipping exon 7. This report expands the genotypic spectrum of LHCGR mutations, with relevant implications for the molecular analysis of this gene.

[Repair and functional reconstruction of the penis (a report of 62 cases)].

OBJECTIVE: To investigate the effects of surgery treatment on serious penile lesions and malformation. METHODS: Sixty-two patients, aged from 19 to 63 years old (mean 35 ys), were included in the study. Among them, 4 patients suffered from penis partial defection were respectively treated with restoring defective penis, penis lengthening and urethroplasty; three patients with penis completely missing were treated with penis reconstruction surgery; 22 cases with serious penile curvature were treated with the 16-dot plication technique (Lue's procedure); 15 cases with penile fracture were treated with conservative treatment for 1 case and with patch penis, corpus spongiosum, and deep penile dorsal vein ligation for 14 cases; 5 cases with post-operative complications of 3-pieces of penile prosthesis, including the prosthesis perforating to the urethra, water pump failure, broken connection tube, erection angle < 60 degrees and failure to expansion the corpus cavernosum, were treated by taking out prostheses, urethral repair cracks, replacement of the prostheses, excision of fibrosis scar and re-implantation prostheses respectively. Four cases with penis complete amputation were treated with the penis replantation; three cases of avulsion injury were treated with the replantation and free flap skin; 6 with Paget's disease of penises were treated with the lesion free skin buried in the scrotum and penis. RESULTS: All these patients were followed up for 3 months to 4 years, with the average of 9 months. Among the 4 cases of penis partial defection, 2 patients were satisfied with the penile appearance and sexual function; 1 got some satisfactory and 1 was unsatisfied. Three cases with the loss of the penis completely were satisfied with both the postoperative appearance and urination, and 1 was not satisfied. Twenty-two cases of penile curvature deformities were corrected, and one case was recurrence. Fourteen of the 15 patients with penile fracture were followed, and all got the restoration of sexual function. Among them, 5 cases with post-operative complications, including mild bending, algopareunia, subcutaneous induration, poor hardness and poor sexual pleasure, were not further treated, and another case lost; Five cases with post-operative complications of three-pieces penile prosthesis were treated successfully, and 4 of their spouses were satisfied with their sexual function after operation, only 1 of their spouse not satisfied. Among four cases with complete amputation of penis, two cases of penis were replanted successfully while two necrosis. Three cases with avulsion were treated with skin grafting successfully. All 6 cases with penile Paget's disease were followed for 2 -4 years, and free skin grafts were all survival. One patient died of brain metastases 18 months after operation and five cases were disease-free survival. CONCLUSION: The patients should be treated based on the procedure of andrological and urological surgery, together with microsurgical, flap or skin graft technique. The urologist should design personalized surgical procedure. Most of the patient's penis shape and erectile dysfunction can be reconstructed by our procedures, but some patients can not achieve the desired appearance or function of penis. New approaches of the treatment ought to be developed to restore both of the shape and function for those severe injury of the penis.

Bone morphogenetic protein 7 enhances the osteogenic differentiation of human dermal-derived CD105+ fibroblast cells through the Smad and MAPK pathways.

The skin, as the largest organ of the human body, is an important source of stromal stem cells with multipotent differentiation potential. CD105+ mesenchymal stem cells exhibit a higher level of stemness than CD105­ cells. In the present study, human dermal­derived CD105+ fibroblast cells (CD105+ hDDFCs) were isolated from human foreskin specimens using immunomagnetic isolation methods to examine the role of bone morphogenetic protein (BMP)­7 in osteogenic differentiation. Adenovirus­mediated recombinant BMP7 expression enhanced osteogenesis­associated gene expression, calcium deposition, and alkaline phosphatase activity. Investigation of the underlying mechanisms showed that BMP7 activated small mothers against decapentaplegic (Smad) and p38/mitogen­activated protein kinase signaling in CD105+ hDDFCs. The small interfering RNA­mediated knockdown of Smad4 or inhibition of p38 attenuated the BMP7­induced enhancement of osteogenic differentiation. In an in vivo ectopic bone formation model, the adenovirus­mediated overexpression of BMP7 enhanced bone formation from CD105+ hDDFCs. Taken together, these data indicated that adenoviral BMP7 gene transfer in CD105+ hDDFCs may be developed as an effective tool for bone tissue engineering.

Somatic mosaicism of androgen receptor gene in an androgen insensitivity syndrome patient conceived through assisted reproduction technique.

BACKGROUND: Mutations of human androgen receptor (AR) gene are responsible for androgen insensitivity syndrome (AIS). Variable phenotypes and androgen receptor binding activity have permitted the classification of AIS into complete (CAIS), partial (PAIS), and minimal or mild (MAIS) forms. Somatic mosaicism in AIS is a rare condition which happened when de novo mutations occur after the zygotic stage. METHODS: Clinical evaluation, hormone measurements, and molecular analysis were performed to diagnose the patient in the study. RESULTS: A 46, XY girl who conceived through in vitro fertilization (IVF), presented with partial virilization of external genitalia, was found to have the p.C620R in heterozygosity. The variant p.C620R of AR has been previously reported in a patient with completely feminized external genitalia, which was inherited from the heterozygote carrier mother. Mutation analysis of the mother of our patient revealed that the variant was de novo and presented as a somatic mosaicism which indicated an insufficient amount of wild-type AR in our patient. CONCLUSION: This is the first case that AIS was caused by de novo mutation of AR in a 46, XY Disorder of Sexual Development (DSD) patient by the assisted reproduction technique (ART). The phenotype of partial virilization could be explained by AR mutation in somatic mosaicism.

Identification of three novel SRD5A2 mutations in Chinese patients with 5α-reductase 2 deficiency.

In this study, we investigated the genetics, clinical features, and therapeutic approach of 14 patients with 5α-reductase deficiency in China. Genotyping analysis was performed by direct sequencing of PCR products of the steroid 5α-reductase type 2 gene (SRD5A2). The 5α-reductase activities of three novel mutations were investigated by mutagenesis and an in vitro transfection assay. Most patients presented with a microphallus, variable degrees of hypospadias, and cryptorchidism. Eight of 14 patients (57.1%) were initially reared as females and changed their social gender from female to male after puberty. Nine mutations were identified in the 14 patients. p.G203S, p.Q6X, and p.R227Q were the most prevalent mutations. Three mutations (p.K35N, p.H162P, and p.Y136X) have not been reported previously. The nonsense mutation p.Y136X abolished enzymatic activity, whereas p.K35N and p.H162P retained partial enzymatic activity. Topical administration of dihydrotestosterone during infancy or early childhood combined with hypospadia repair surgery had good therapeutic results. In conclusion, we expand the mutation profile of SRD5A2 in the Chinese population. A rational clinical approach to this disorder requires early and accurate diagnosis, especially genetic diagnosis.

[Reconstruction of extended skin defect after the radical resection procedure for penile scrotum skin cancer].

OBJECTIVES: To investigate the reconstruction of skin defect after extended resection of malignant skin tumor in or adjacent to the genitals, and to investigate the recovery of the function of urinary system and sexual intercourse after the operation. METHODS: From February 1998 to August 2006, 17 patients with carcinoma of sweat gland or Paget's disease in or adjacent to the genitals were given standard radical resections including groin lymph node dissections. The deformation of penis were corrected with the split-thickness skin grafts. RESULTS: A large split-thickness skin to cover the wound gave a good result. More than 95% of the skin survived, and the shape and function were perfect. CONCLUSIONS: It is a simple and easy way to repair the skin defect. And the patients have a normal shape and function of genitals. The erectile function and the ability of sexual intercourse is good.

A New Surgical Procedure for Penile Reconstruction by Combined Free Radial Forearm Flap and Dorsalis Pedis Flap.

OBJECTIVE: To introduce a new surgical procedure for penile reconstruction, emphasizing both the aesthetic appearance and the function by combined free radial forearm flap and dorsalis pedis flap. PATIENTS AND METHODS: In this procedure, the penis was subdivided into 2 anatomic subunits: the penile shaft and the glans penis. A sequential innervated radial forearm free flap was combined with a dorsalis pedis free flap to reconstruct the penile shaft and the glans, separately. Cartilage prosthesis was implanted at the same time. Since May 2011, 14 biologically male patients with total penile losses by various reasons were treated with this procedure. Patient satisfaction was evaluated by questionnaire, and sensory testing was performed. RESULTS: The ages of the patients ranged between 21 and 53 years (mean, 35.2 years). The average follow-up period was 38.1 months (range, 25.5-56 months). Twenty-five flaps in 11 patients were 100% viable. One dorsalis pedis flap in a patient underwent partial necrosis. There were no cases of urethral fistula or urethral stenosis, but 1 case of prosthesis infection and 1 case of abdominal hernia were recorded. The sensation of the neophallus recovered 3-6 months after surgery, and the patient satisfaction rate was quite high. CONCLUSION: The new surgical procedure of combined free radial forearm flap and dorsalis pedis flap for penile reconstruction achieves both satisfactory aesthetic and functional results. We recommend this procedure as an alternative ideal method for total penile reconstruction.

Aromatase deficiency: a novel compound heterozygous mutation identified in a Chinese girl with severe phenotype and obvious maternal virilization.

BACKGROUND: Aromatase deficiency is a rare autosomal recessive disorder that is caused by an impairment of androgen conversion to estrogens. Affected 46, XX individuals generally present with virilization of external genitalia at birth and mutations in CYP19A1 gene. OBJECTIVE: This study described the clinical features and molecular basis of a Chinese 46, XX girl born with ambiguous genitalia and investigated the functional alteration of two novel mutations of the CYP19A1 gene. METHODS AND RESULTS: Obvious prepartum virilization and remarkably elevated testosterone were observed in the mother, who was initially suspected to have a testosterone-producing ovarian tumor. Clinical phenotypes and hormone profiles of the patient and her mother were investigated. Genotyping analyses of the CYP19A1 gene were performed in the patient and her parents. Functional impairment of the mutations was explored using three-dimensional computer model and mutagenesises in vitro transfection assays. A compound heterozygous mutation of the CYP19A1 gene was revealed in the patient, with a G deletion in nucleotide 264 of exon 3 in one allele and a 23-bp insertion in exon 9 in another allele; both mutations resulted in reading frame-shifts that led to truncated proteins of 87 and 360 amino acids, respectively. Molecular modeling analysis suggested that the two renascent truncated proteins lacked crucial amino acids that were involved in substrate access and catalysis as well as heme-binding region. Functional studies in transfected HEK-293T cells exhibited a nearly complete abolishment of enzyme activity, which may underlie the phenotype and hormone profile. CONCLUSIONS: Two novel CYP19A1 mutations were identified in a Chinese girl born with ambiguous genitalia and severe maternal virilization during pregnancy. Maternal virilization should prompt consideration of aromatase deficiency, preventing unnecessary interventions in pregnancy. This study broadens the spectrum of phenotype and genetic mutations of this rare disorder.