2002 Bill Reed
International Travel Fellowship

Eli Sprecher, M.D., 5th year resident in the Department of Dermatology at Rambam Medical Center, Technion - Israel Institute of Technology, was the winner of the Everett C. Fox Residents/Fellows Award at the 60th Annual American Academy of Dermatology Meeting.  He was awarded the International Travel Fellowship from the Friends of Bill Reed Club and will give the Bill Reed Lecture at a future meeting.

Introduction:  Congenital hypotrichosis with juvenile macular dystrophy (HJMD; MIM 601553) is an autosomal recessive disorder characterized by hair loss at an early age followed by macular dystrophy eventually leading to blindness during the second decade of life.  Although the disorder has often been described, the small size of the families reported so far has precluded further investigation of the genetic basis of this syndrome. 
Methods:  We have recently identified 5 multiplex families comprising a total of 14 patients affected by HJMD.  The present study was aimed at investigating the molecular basis of HJMD in these families in 3 stages: (1) Clinical characterization of the syndrome; (2) Localization of the HJMD gene locus using homozygosity mapping; (3) Identification of the defective gene in HJMD using candidate gene positional cloning. 
Results:  All patients were born with normal hair at birth; hair loss occurred at the age of 3 months and partial regrowth of sparse and short hair was observed during puberty.  Light and scanning electron microscopy revealed unique and previously unreported structural abnormalities of the hair shaft.  Eye fundus examination showed different degrees of macular changes from fine pigmentary dispersion to prominent atrophic scars.  Electrophysiological evaluation of the visual system indicated impaired macular function.  A genome-wide screening was performed using 202 microsatellite markers.  The disease phenotype demonstrated linkage to a novel locus on 16q22.1 with a maximal LOD score of 10.4 at marker D16S2624.  Through further haplotype analysis, we identified a 5 cM critical interval for the disease gene.  We characterized three contigs linked to this region and containing approximately 45 genes.  One of these contigs harbored the CDH3 gene encoding P-cadherin, which is expressed in retinal pigment epithelium and hair follicles and mediates cell-cell adhesion at the adherens junction.  Mutation analysis revealed in all families a common homozygous deletion in exon 8 of the CDH3 gene, resulting in the translation of a markedly truncated protein.  The fact that patients of apparently unrelated families shared an ancestral haplotype suggests a founder effect for this mutation. 
Conclusions:  The present results establish the molecular etiology of HJMD.  They implicate for the first time a member of the cadherin family in the pathogenesis of a hair disorder, reveal an hitherto unrecognized functional/developmental link between hair follicle and retinal pigment epithelia and point to a novel therapeutic target for more common inherited and acquired hair and retinal disorders. 

2001 Bill Reed Lecture

Nicole F. Hayre, M.D., Resident in the Department of Dermatology at the Washington Hospital Center, was the winner of the Everett C. Fox Residents/Fellows Award at the 59th Annual American Academy of Dermatology Meeting.  She was awarded the International Travel Fellowship from the Friends of Bill Reed Club.

Early identification of metastases in patients with melanoma is critical. We developed a nested RT-PCR assay for detection of tyrosinase (tyr) mRNA by real-time fluorescent RT-PCR. Consistent detection of tyr negative RNA spiked with tyr positive RNA from malignant melanoma cells was achieved. Total RNA was extracted from blood of 17 patients with stage IB-IV melanoma. All 4 stage IV patients tested positive while both stage IB patients tested negative. One of 9 patients with lymph node metastases identified only by tyr RT-PCR on node tissue was positive, consistent with rates of disease progression. One stage IV patient with a positive assay prior to and during treatment converted to a negative result at the time of radiographical remission. We next developed a novel quantitative RT-PCR assay to detect tyr mRNA in blood using our primer pair and flourescent probe. Using spiked RNA, a sensitivity of 100 cells per ml of blood was achieved. We are currently applying this quantitative assay clinically. In summary, we developed a nested PCR assay with potential clinical utility, and a novel quantitative tyr mRNA assay for further testing. Our goal is to develop a blood test that will improve the initial staging of melanoma, allow for better monitoring of disease progression, and ultimately result in more timely and effective therapy.

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PSRC 1999 Current Discussions

Web-based Teledermatology Consult System; preliminary Results from the First One hundred Cases by Hon S. Pak, MD, Walter Reed Army Medical Center.
 

A Role for CD40-CD40 Ligand Interactions in the Generation of Type 1 Cytokine Responses in Human Leprosy by Paul S. Yamauchi, MD, PhD, University of California, Los Angeles.
 

Teledermatoscopy in Switzerland by R.P. Braun, MD, and J.H. Saurat, MD, Univ. Hospital Geneva and DHURDV, Geneva/Lausanne.