Variable expression pattern in Donnai-Barrow syndrome: Report of two novel LRP2 mutations and review of the literature.

• 影响指数: 2.465
• 发表时间: May 2015
• 来源期刊: Eur J Med Genet
• DOI: 10.1016/j.ejmg.2014.12.008
• PMID: 25682901
• 文章类型: Journal Article
• 中科院分区: Q3
• 方向: 生物
• 作者列表: Khalifa O,Al-Sahlawi Z,Imtiaz F,Ramzan K,Allam R,Al-Mostafa A,Abdel-Fattah M,Abuharb G,Nester M,Verloes A,Al-Zaidan H

关键词: Agenesis of corpus callosum; Congenital diaphragmatic hernia; Donnai-Barrow syndrome; Hypertelorism; Omphalocele; Sensorineural hearing loss

Mesh: Adolescent; Agenesis of Corpus Callosum / genetics metabolism; Child; Child, Preschool; Codon, Nonsense; DNA Mutational Analysis; Female; Gene Expression; Hearing Loss, Sensorineural / genetics metabolism; Hernias, Diaphragmatic, Congenital / genetics metabolism; Humans; Infant; Infant, Newborn; Low Density Lipoprotein Receptor-Related Protein-2 / genetics metabolism; Male; Mutation, Missense; Myopia / genetics metabolism; Proteinuria / genetics metabolism; Renal Tubular Transport, Inborn Errors / genetics metabolism; Young Adult

Abstract

Donnai-Barrow syndrome (DBS; MIM 222448) is characterized by typical craniofacial anomalies (major hypertelorism with bulging eyes), high grade myopia, deafness and low molecular weight proteinuria. The disorder results from mutations in the low density lipoprotein receptor-related protein 2 gene LRP2 that maps to chromosome 2q31.1. LRP2 encodes megalin, a multi-ligand endocytic receptor. Herein, we describe the clinical presentation of 4 patients from 2 unrelated Saudi families. Two novel LRP2 mutations, a homozygous nonsense mutation (c.4968C>G; p.Tyr1656*) and a missense mutation (c.12062G>A; p.Cys4021Tyr), were detected in the first and second family respectively. Interestingly, intrafamilial phenotypic variability was observed in one family, while DBS features were atypical in the second family. Differential diagnosis of DBS includes several syndromes associating hypertelorism with high grade myopia, and several syndromal forms of CDH, which are briefly summarized in this study.