Information on all the types of lymphangiectasia, including intestinal, pulmonary, renal, cutaneous (skin). Sponsored by Pat O'Connor

Friday, June 27, 2008

HGF and MET Mututations involving lymphangiectasia

HGF and MET Mutations in Primary and Secondary Lymphedema.
Lymphat Res Biol. 2008
inegold DN, Schacht V, Kimak MA, Lawrence EC, Foeldi E, Karlsson JM, Baty CJ, Ferrell RE.

Department of Human Genetics, University of Pittsburgh, Pittsburgh, Pennsylvania., Department of Pediatrics, University of Pittsburgh, Pittsburgh, Pennsylvania., DNF, CJB, and REF contributed equally to this work.

Abstract Background: Lymphedema is the abnormal accumulation of protein-rich fluid in the interstitial space. Primary lymphedema is a rare genetic condition with both autosomal dominant and autosomal recessive modes of inheritance.

Three genes, FLT4 (VEGFR3), FOXC2, and SOX18 cause varying forms of primary lymphedema. In industrialized countries, secondary lymphedema is usually associated with cancer therapy and/or trauma. Recent observations suggested that hepatocyte growth factor/high affinity hepatocyte growth factor receptor (HGF/MET) were new candidate lymphedema genes.

Methods and Results: The coding exons and flanking regions of HGF and MET were directly sequenced in 145 lymphedema probands, 59 unrelated women with secondary lymphedema following treatment for breast cancer, 21 individual patients with lymphedema and intestinal lymphangiectasia, and at least 159 unrelated ethnic matched control individuals. Mutations leading to truncation or missense changes in evolutionarily conserved residues of HGF and MET were identified. These mutations were not polymorphic in control individuals.

Conclusions:The identification of HGF/MET mutations in primary lymphedema, lymphedema/lymphangiectasia, and breast cancer-associated secondary lymphedema suggests that the HGF/MET pathway is causal or alters susceptibility for a broad range of lymphedema phenotypes. The HGF/MET pathway provides a new target for the prevention and/or treatment of lymphedema.

Mary Ann Liebert


Tuesday, June 10, 2008

Congenital Lymphedema-lymphangiectasia Associated With Scrotal Angiokeratoma (Fordyce Type) and Hearing Impairment.

Congenital Lymphedema-lymphangiectasia Associated With Scrotal Angiokeratoma (Fordyce Type) and Hearing Impairment.

J Clin Gastroenterol. 2008 May

Pavone P, Lucenti C, Fraggetta F, Micali G, Incorpora G, Ruggieri M.
Departments of *Paediatrics §Dermatology, University of Catania †Department of Paediatrics, AUSL 3, Caltagirone ‡Pathology Unit, AUSL 3, Cannizzaro Hospital ∥Institute of Neurological Science, National Research Council, Catania, Italy.

Congenital lymphangiectasia-lymphedema is a rare disorder that presents with
edema of the lower half of the body, the face, hands, and scrotum, or with protein-losing enteropathy owing to structural anomalies in the endothelium of the lymphatic system. We describe a biopsy-proven case of severe lymphangiectasia-lymphedema in a 16-year-old boy who was born to consanguineous parents and who, in addition, had mild (20 to 40 dB), early onset, sensorineural deafness and skin abnormalities, consisting of angiokeratomas of the face, hands, and feet, and also a large, localized angiokeratoma of the scrotum and the penis (Fordyce type). Both of the proband's parents had profound (>80 dB), congenital, mixed conductive/sensorineural, nonsyndromic deafness to low-mid frequencies. To the best of our knowledge, this constellation of lymphatic, skin, hearing, and systemic abnormalities seen in the proband has not been previously reported.


Labels: ,