The spectrum of phenotypes associated with mutations in steroidogenic factor 1 (SF-1, NR5A1, Ad4BP) includes severe penoscrotal hypospadias in 46,XY males without adrenal insufficiency

OBJECTIVE. Hypospadias is a frequent congenital anomaly but in most cases an underlying cause is not found. Steroidogenic factor 1 (SF-1, NR5A1, Ad4BP) is a key regulator of human sex development and an increasing number of SF-1 (NR5A1) mutations are reported in 46,XY disorders of sex development (DSD). We hypothesized that NR5A1 mutations could be identified in boys with hypospadias. DESIGN AND METHODS. Mutational analysis of NR5A1 in 60 individuals with varying degrees of hypospadias from the German DSD network. RESULTS. Heterozygous NR5A1 mutations were found in three out of 60 cases. These three individuals represented the most severe end of the spectrum studied as they presented with penoscrotal hypospadias, variable androgenization of the phallus and undescended testes (three out of 20 cases (15%) with this phenotype). Testosterone was low in all three patients and inhibin B/anti-Müllerian hormone (AMH) were low in two patients. Two patients had a clear male gender assignment. Gender re-assignment to male occurred in the third case. Two patients harbored heterozygous nonsense mutations (p.Q107X/WT, p.E11X/WT). One patient had a heterozygous splice site mutation in intron 2 (c.103-3A/WT) predicted to disrupt the main DNA-binding motif. Functional studies of the nonsense mutants showed impaired transcriptional activation of an SF-1-responsive promoter (Cyp11a). To date, adrenal insufficiency has not occurred in any of the patients. CONCLUSIONS. SF-1 (NR5A1) mutations should be considered in 46,XY individuals with severe (penoscrotal) hypospadias, especially if undescended testes, low testosterone, or low inhibin B/AMH levels are present. SF-1 mutations in milder forms of idiopathic hypospadias are unlikely to be common

14-Bromo-12-chloro-2,16-dioxapentacyclohenicosa-3(8),10,12,14-tetraene-7,20-dione

In the title compound, C19H16BrClO4, both the fused xanthene rings and one of the cyclohexane rings adopt envelope conformations, while the other cyclohexane ring is in a chair conformation. In the crystal, molecules are linked by C-H...O hydrogen bonds, forming infinite chains running along [10-1] incorporating R22(16) ring motifs. In addition, C-H...[pi] interactions and weak [pi]-[pi] stacking interactions [centroid-centroid distance = 3.768 (3) Å] help to consolidate the packing

2,2′-[(E,E)-cis-(Cyclo­hexane-1,4-di­yl)bis­(nitrilo­methanylyl­idene)]diphenol

In the title compound, C20H22N2O2, the asymmetric unit contains two independent half-mol­ecules, which are both completed by crystallographic inversion symmetry. The cyclo­hexane rings of both mol­ecules adopt chair conformations; the N atoms are in equatorial orientations in one mol­ecule and in axial orientations in the other. Both mol­ecules feature two intra­molecular O—H⋯N hydrogen bonds, which generate S(6) rings

Crystal structure of ethyl 2-[2-((1E)-{(1E)-2-[2-(2-ethoxy-2-oxoethoxy)benzyl-idene]hydrazin-1-ylidene}methyl)phen-oxy]acetate

NSF–MRI grant No. 1228232 for the purchase of the diffractometer and Tulane University for support of the Tulane Crystallography Laboratory are gratefully acknowledged.Peer reviewedPublisher PD

2-((E)-{[4-(Hy­droxy­meth­yl)phen­yl]imino}­meth­yl)phenol

The title compound, C14H13NO2, adopts the enol–imine tautomeric form, with an intra­molecular O—H⋯N hydrogen bond which generates an S(6) ring motif. The dihedral angle between the aromatic rings is 7.85 (7)°. The crystal structure is stabilized by O—H⋯O, O—H⋯N and C—H⋯O hydrogen bonds, forming a two-dimensional array that stacks along the a axis. In addition, a C—H⋯π inter­action contributes to the stabilization of the crystal packing

(6Z)-4-Bromo-6-{[(2-hy­droxy­eth­yl)amino]­methyl­idene}cyclo­hexa-2,4-dien-1-one

The title mol­ecule, C9H10BrNO2, excluding methyl­ene H atoms and the C—OH group, is essentially planar, with a maximum deviation of 0.037 (2) Å for the N atom. The N—C—C—O torsion angle is −63.1 (3)°. The mol­ecular structure is stabilized by a weak intra­molecular N—H⋯O(carbonyl) hydrogen bond, forming an S(6) motif. In the crystal, mol­ecules are linked by O—H⋯O and C—H⋯O hydrogen bonds, forming a three-dimensional network

1-{6-Chloro-2-[(2-chloro-8-methyl-3-quinol­yl)meth­oxy]-4-phenyl­quinolin-3-yl}ethanone

In the title mol­ecule, C28H20Cl2N2O2, the dihedral angle between the 2-chloro­quinoline and 6-chloro­quinoline rings is 7.55 (6)°. The dihedral angle between the phenyl ring and its attached quinoline ring is 62.59 (4)°. In the crystal, aromatic π–π stacking inter­actions [centroid–centroid distances = 3.771 (3) and 3.612 (3) Å] help to establish the packing

7-Bromo-9-(2-hy­droxy-4,4-dimethyl-6-oxocyclo­hex-1-en-1-yl)-3,3-dimethyl-2,3,4,9-tetra­hydro-1H-xanthen-1-one

In the xanthene ring system of the title compound, C23H25BrO4, the 4H-pyran ring is almost planar [maximum deviation = 0.040 (3) Å] and the cyclo­hexene ring adopts a sofa conformation. The cyclo­hexene ring attached to the xanthene system is puckered [Q T = 0.427 (3) Å, θ = 55.0 (4) ° and ϕ = 164.4 (6) °]. In the crystal, mol­ecules are linked to each other by O—H⋯O and C—H⋯O hydrogen bonds

Oxomemazine hydro­chloride

In the title compound [systematic name: 3-(5,5-dioxo­phen­othia­zin-10-yl)-N,N,2-trimethyl­propanaminium chloride], C18H23N2O2S+·Cl−, the dihedral angle between the two outer aromatic rings of the phenothia­zine unit is 30.5 (2)°. In the crystal, the components are linked by N—H⋯Cl and C—H⋯Cl hydrogen bonds and C—H⋯π inter­actions

(2Z)-2-(4-Methyl­phen­yl)-3-(2-naphth­yl)prop-2-enenitrile

In the title compound, C20H15N, the dihedral angle between the naphthalene and benzene rings is 60.30 (16)°. The crystal packing features very weak inter­molecular C—H⋯π inter­actions