Hypotrichosis‐lymphedema‐telangiectasia‐renal defect associated with a truncating mutation in the SOX18 gene

  title={Hypotrichosis‐lymphedema‐telangiectasia‐renal defect associated with a truncating mutation in the SOX18 gene},
  author={Sharon Moalem and Pascal Brouillard and Dirk R J Kuypers and Eric Legius and E. Harvey and Graham Taylor and Mathias Francois and Miikka Vikkula and David Chitayat},
  journal={Clinical Genetics},
SOX18 mutations in humans are associated with both recessive and dominant hypotrichosis–lymphedema–telangiectasia syndrome (HLTS). We report two families with affected children carrying a SOX18 mutation: a living patient and his stillborn brother from Canada and a Belgian patient. The two living patients were diagnosed with HLTS and DNA analysis for the SOX18 gene showed that both had the identical heterozygous C > A transversion, resulting in a pre‐mature truncation of the protein, lacking the… 
A novel autosomal dominant mutation in SOX18 resulting in a fatal case of hypotrichosis–lymphedema–telangiectasia syndrome
A neonate with a novel mutation in SOX18 is reported presenting with cardinal features of HLTS in addition to unique findings of severe chylothorax and relentless pulmonary hypertension that culminated in death.
Hypotrichosis‐lymphedema‐telangiectasia syndrome: Report of ileal atresia associated with a SOX18 de novo pathogenic variant and review of the phenotypic spectrum
These phenotypic variations are summarized and an additional HLTS patient is reported, with a 14‐nucleotide de novo duplication in SOX18 and congenital ileal atresia, a feature not previously associated with HLTS.
Molecular and Genetic Aspects of Hemangiomas and Vascular Malformations
Expression profiling and functional studies, in vitro and in animal models, have in parallel begun to uncover how the aberrant genes affect the different cellular and molecular components of the vasculature.
Personalized Therapy for Generalized Lymphatic Anomaly/Gorham-Stout Disease With a Combination of Sunitinib and Taxol
Both patients experienced clinical and radiologic response without major toxicities, suggesting that patients with rare conditions may benefit from individualized, molecularly based therapies.
Genetic causes of lymphedema
An extensive review of the literature regarding the genes and clinical presentations associated with primary lymphedema is performed, and a panel approach to screen all genes at once is likely the most efficient approach for diagnosis.
R-propranolol is a small molecule inhibitor of the SOX18 transcription factor in a rare vascular syndrome and hemangioma
This work reports successful treatment of pericardial edema with propranolol in a patient with Hypotrichosis-Lymphedema-Telangiectasia and Renal (HLTRS) syndrome, caused by a mutation in SOX18, and suggests R(+)-propr ethanol repurposing to numerous indications ranging from vascular diseases to metastatic cancer.


Mutations in the transcription factor gene SOX18 underlie recessive and dominant forms of hypotrichosis-lymphedema-telangiectasia.
It is shown that SOX18 mutations in humans cause both recessive and dominant hypotrichosis-lymphedema-telangiectasia, suggesting that, in addition to its established role in hair and blood vessel development, theSOX18 transcription factor plays a role in the development and/or maintenance of lymphatic vessels.
Mutations in CCBE1 cause generalized lymph vessel dysplasia in humans
Homozygous and compound heterozygous mutations in seven subjects paired with functional analysis in a zebrafish model identify CCBE1 as one of few genes causing primary generalized lymph-vessel dysplasia in humans.
Mutations in SOX17 are Associated with Congenital Anomalies of the Kidney and the Urinary Tract
The data indicate a role of SOX17 in human kidney and urinary tract development and implicate theSOX17–p.Y259N mutation as a causative factor in CAKUT.
Vascular defects in a mouse model of hypotrichosis-lymphedema-telangiectasia syndrome indicate a role for SOX18 in blood vessel maturation.
The results indicate that vascular anomalies in HLT arise from defects in regulation of genes required for the acquisition of structural integrity during microvascular maturation.
Genetics of lymphatic anomalies.
Germline mutations have been identified in at least 20 genes that encode proteins acting around VEGFR-3 signaling but also downstream of other tyrosine kinase receptors that explain more than a quarter of the incidence of primary lymphedema, mostly of inherited forms.
Cutaneous telangiectasia, sparse hair and membranoproliferative glomerulonephritis
A boy with sparse red hair, absent eye-brows and eyelashes, cutaneous telangiectasia, poorly developed subcutaneous fat and normocomplementaemic membranoproliferative glomerulonephritis is described.
Mutations in Sox18 underlie cardiovascular and hair follicle defects in ragged mice
It is found that Sox18 is expressed in the developing vascular endothelium and hair follicles in mouse embryos, and this region contains point mutations in Sox18 in two different Ra alleles that result in missense translation and premature truncation of the encoded protein.
Dominantly inherited glomerulonephritis and an unusual skin disease.
An unusual association of uncommon facies including telangiectasia in a butterfly distribution, a similar skin lesion on extensor areas, sparse hair, and membranoproliferative glomerulonephritis is
Cutaneous telangiectasias, sparse hair, and type I membranoproliferative glomerulonephritis
Abstract We report the unusual association of normocomplementemic type I membranoproliferative glomerulonephritis in a 10-year-old girl with sparse red hair, absent eyebrows and eyelashes, cutaneous
Redundant roles of Sox17 and Sox18 in postnatal angiogenesis in mice
In vitro angiogenesis assays showed that the Sox17+/--Sox18-/- endothelial cells were defective in endothelial sprouting and remodeling of the vasculature in a phenotype-dependent manner, indicating that Sox17 and Sox18, and possibly all three SoxF genes, are cooperatively involved in mammalian vascular development.