Familial incontinentia pigmenti (IP) is a rare X-linked dominant disorder that affects ectodermal tissues. Over 90% of IP carrier females have a recurrent genomic deletion of exons 4-10 of the NEMO (IKBKG-IKKgamma) gene, which encodes a regulatory component of the IkB kinase complex, required to activate the NF-kB pathway. In IP, mutations in NEMOlead to the complete loss of NF-kB activation creating a susceptibility to cellular apoptosis in response to TNF-alpha. This condition is lethal for males during embryogenesis while females, who are mosaic as a result of X-inactivation, can survive. Recently, a second nonfunctional copy of the gene, DeltaNEMO, was identified, opposite in direction to NEMO in a 35.5-kb duplicated sequence tract. PCR-based detection of the NEMO deletion is diagnostic for IP disease. However, we present instances in which ex 4-10 DeltaNEMO pseudogene deletion occurs in unaffected parents of two females with clinically characteristic IP. These were missed by the currently standard PCR-based method, but can be easily discriminated by a new PCR-based test reported here that permits unambiguous molecular diagnosis and proper familial genetic counseling for IP.

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The crystal structure, thermal vibrations and electron density of L-arginine phosphate monohydrate (formally C6H15N4O2 +.H2PO4 −.H2O) have been analysed using 130 K single-crystal X-ray diffraction data to a resolution of (sin θ/λ)max = 1.20 Å−1. A multipolar pseudo-atom density model was fitted against the 6805 observed data with I > 3σ(I), [R(F) = 0.016,Rw (F) = 0.014, S = 1.39] in order to map the static valence-electron density distribution. Positional and thermal vibration parameters for H atoms were taken from neutron diffraction results. A comparison between the electron density ρ(r), ∇2 ρ(r) and the electrostatic potential calculated from X−X and X−(X + N) refinements shows that reliable results may be obtained from X−X data only.

Articles you may be interested inElectronic structure determination and dynamical properties of iron (II)guanosine5'monophosphate complex via mossbauer and magnetic susceptibility measurements J. Chem. Phys. 92, 6131 (1990); 10.1063/1.458336 Electron density studies of porphyrins and phthalocyanines. IV. Electron density distribution in crystals of (meso tetraphenylporphinato) iron(II) J. Chem. Phys. 84, 6969 (1986); 10.1063/1.450617 Electron density studies of porphyrins and phthalocyanines. III. The electronic ground state of iron(II) phthalocyanine J. Chem. Phys. 81, 1983 (1984); 10.1063/1.447821 Spin S = 1 in sixcoordinated iron(II): Lowtemperature magnetism, Mössbauer effect, and electronic structureMossbauer and magnetic susceptibility measurements of iron(lI) phthalocyanine in the temperature range between 77 and 300 K have been c::.:ried out. The crystal field parameters and the electronic structure of the Fe(lI) ion have been obtained using a least-squares fitting procedure of the dependence on the temperature of both magnetic susceptibility and quadrupole splitting. It is concluded that the ground state has major 3 A character.

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