आणविक और आनुवंशिक चिकित्सा

Donnai– Barrow Syndrome in Two Sisters with a Homozygous LRP2 Mutation and Renal Dysfunction. Integral Management of the Disease with Review of the Literature.

Abstract

Peces R, Santos-Simarro F, Palomares-Bralo M, Peces C, Rufo V, Solís-López M, Mena R, Selgas R, Lapunzina P and Nevado J

Objectives: Donnai–Barrow syndrome (DBS) or facio oculo acoustic renal (FOAR) syndrome, DBS/FOAR (MIM# 227290) is caused by mutations in the LRP2 gene (MIM# 600073). Disease severity and penetrance vary greatly among patients carrying the same pathogenic variant(s) and single-gene variants often do not reliably predict the disease phenotypes.
Background: The LRP2 gene located on chromosome 2q31.1 band encodes megalin, a multi-ligand endocytic receptor. There are less than 50 cases reported worldwide.
Cases presentation: We report two Ecuadorian sisters born from consanguineous parents carrying a homozygous LRP2 mutation in intron 44 NM_004525.2:c.8452+1G>A. Both individuals, aged 23 and 20 years respectively, presented classical clinical features of the DBS/FOAR including craniofacial dysmorphology, hypertelorism, ocular anomalies, cataracts, high myopia, and sensorineural deafness associated with renal dysfunction (proteinuria, hypercalciuria and hypocitraturia). Both sisters were treated with hearing aids, cochlear implants, corrective lenses, cataracts surgery, vitamin D and potassium citrate supplementation, and renal protection with angiotensin II receptor antagonists.
Conclusion: As far as we know, this is the first family of DBS/FOAR resulting from consanguineous parents with a LRP2 splice site mutation NM_004525.2:c.8452+1G>A, with a complete characterization of the renal phenotype and follow-up.