A trinucleotide deletion in the transthyretin gene (delta V 122) in a kindred with familial amyloidotic polyneuropathy

A 63-year-old white man of Ecuadorian origin had a subarachnoid hemorrhage at age 57 followed by numbness and paresthesia in his lower extremities. He subsequently developed sexual impotence, alternating constipation and diarrhea, urinary frequency, and difficulty in walking. Rectal biopsy revealed amyloid deposits immunohistochemically reactive with antitransthyretin antisera. Direct DNA sequencing of the transthyretin gene of the patient showed a trinucleotide deletion in exon 4. This deletion resulted in the loss of one of two valines at position 121 or 122. DNA analysis on 11 family members at risk revealed four mutant gene carriers. Plasma transthyretin levels in the mutant gene carriers measured by nephelometry were very low. Peptide sequence analysis revealed that most of plasma transthyretin was normal with only a small amount of variant protein. This is the first report of a DNA deletion in the transthyretin gene. We speculate that the loss of valine in the carboxyl terminal region of the transthyretin monomer alters stability of the tetrameric protein, which leads to rapid clearance from the plasma and amyloid deposition in the tissue.     

A robust 43-GHz VCO in CMOS for OC-768 SONET applications

In this paper, we present a 43-GHz LC-VCO in 0.13-/spl mu/m CMOS for use in SONET OC-768 optical networks. A tuned output buffer is used to provide 1.3 V/sub p-p/ (single-ended) into a 90-fF capacitive load as is required when the VCO is used in typical clock and data recovery (CDR) circuits. Phase noise is -90 dBc/Hz at a 1-MHz offset from the carrier; this meets SONET jitter specifications. The design has a tune range of 4.2%. The VCO, including output buffers, consumes 14 mA from a 1-V supply and occupies 0.06 mm/sup 2/ of die area. Modern CMOS process characteristics and the high center frequency of this design mean that the tank loss is not dominated by the integrated inductor, but rather by the tank capacitance. An area-efficient inductor design that does not require any optimization is used.