Abstract
Hereditary lymphedema is a rare, lymphatic disorder resulting in the chronic swelling of the extremities. It shows wide inter- and intra-familial clinical heterogeneity as well as variability in the age of onset. There are more than four genetically distinct lymphedema conditions known and mutations in three genes have been discovered in families with lymphedema. However, many other familial lymphedemas do not show linkage with the known loci, suggesting genetic heterogeneity. Here, we describe a large inbred Pakistani family with congenital, progressive lymphedema confined to the lower limbs, which fades away at 40-45 years of age. This condition segregates in an autosomal dominant fashion with reduced penetrance. The features are close to primary lymphedema I, Nonne-Milory type (MIM 153100). We exclude this condition for linkage to the known loci for lymphedema by employing highly polymorphic microsatellite markers from these intervals. Then, through a genome-wide linkage study we show that the malformation in our family maps to chromosome 6q16.2-q22.1. The highest pair-wise LOD score (Z(max) = 3.19) was obtained with microsatellite marker D6S1671, and a multipoint score of 3.75 was obtained at 108 cM. Haplotype analysis indi...Continue Reading
References
Oct 29, 1992·Nature·J WeissenbachM Lathrop
Aug 1, 1985·Journal of Medical Genetics·R F Dale
Mar 14, 1996·Nature·C DibJ Weissenbach
Jun 23, 1998·American Journal of Human Genetics·J R O'Connell, D E Weeks
Aug 27, 1998·American Journal of Human Genetics·K W BromanJ L Weber
Nov 18, 1998·Human Molecular Genetics·R E FerrellD N Finegold
Feb 11, 1999·American Journal of Human Genetics·A L EvansM Sarfarazi
Jun 3, 2000·Nature Genetics·M J KarkkainenD N Finegold
Jun 17, 2000·American Journal of Human Genetics·A IrrthumM Vikkula
Nov 15, 2000·American Journal of Human Genetics·J FangT W Glover
May 24, 2001·Human Molecular Genetics·D N FinegoldR E Ferrell
Jul 13, 2002·Journal of Medical Genetics·G BriceV A Murday
Aug 10, 2002·Bioinformatics·M Fishelson, D Geiger
Apr 25, 2003·The Journal of Pediatrics·Martin FrühwirthHelmut Ellemunter
May 13, 2003·American Journal of Human Genetics·Alexandre IrrthumMiikka Vikkula
Oct 16, 2004·American Journal of Human Genetics·X KongT C Matise
Feb 4, 2005·Journal of Medical Genetics·G BriceP Mortimer
Aug 23, 2006·Journal of Human Genetics·Ronen SpiegelStavit A Shalev
Sep 13, 2006·Clinical Genetics·A GhalamkarpourM Vikkula
Citations
Mar 20, 2009·Human Molecular Genetics·Nisha LimayeMiikka Vikkula
Nov 26, 2010·Clinics in Plastic Surgery·Laurence M BoonMiikka Vikkula
Jun 29, 2010·American Journal of Medical Genetics. Part a·Mary C O'DriscollKaren W Gripp
Apr 10, 2014·Case Reports in Medicine·Jose Maria Pereira de GodoyMaria de Fatima Guerreiro Godoy
Mar 11, 2017·Plastic and Reconstructive Surgery. Global Open·Jeremy A GossArin K Greene
Sep 16, 2014·Journal of Pediatric Hematology/oncology·Julie BlattArthur S Aylsworth
Mar 25, 2017·Case Reports in Pediatrics·Livia Maria Pereira de GodoyMaria de Fátima Guerreiro Godoy