title: Variable expression pattern in Donnai-Barrow syndrome: Report of two novel LRP2 mutations and review of the literature.
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.
authors: Department of Medical Genetics, King Faisal Specialist Hospital and Research Centre, Riyadh, Saudi Arabia; Department of Pediatrics, Clinical Genetics Unit, Faculty of Medicine, Ain Shams University, Cairo, Egypt. Electronic address: olaali@kfshrc.edu.
authors: Ola
authors: O
authors: Khalifa
authors: Department of Medical Genetics, King Faisal Specialist Hospital and Research Centre, Riyadh, Saudi Arabia.
authors: Zahra
authors: Z
authors: Al-Sahlawi
authors: Department of Genetics, King Faisal Specialist Hospital and Research Centre, Riyadh, Saudi Arabia.
authors: Faiqa
authors: F
authors: Imtiaz
authors: Department of Genetics, King Faisal Specialist Hospital and Research Centre, Riyadh, Saudi Arabia.
authors: Khushnooda
authors: K
authors: Ramzan
authors: Department of Genetics, King Faisal Specialist Hospital and Research Centre, Riyadh, Saudi Arabia.
authors: Rabab
authors: R
authors: Allam
authors: Department of Genetics, King Faisal Specialist Hospital and Research Centre, Riyadh, Saudi Arabia.
authors: Abeer
authors: A
authors: Al-Mostafa
authors: Department of Ophthalmology, King Faisal Specialist Hospital and Research Centre, Riyadh, Saudi Arabia; Department of Ophthalmology, Faculty of Medicine, Cairo University, Cairo, Egypt.
authors: Maaly
authors: M
authors: Abdel-Fattah
authors: Department of Otolaryngology/Head and Neck Surgery and Communication Sciences, Section of Audiology, King Faisal Specialist Hospital and Research Centre, Riyadh, Saudi Arabia.
authors: Gheid
authors: G
authors: Abuharb
authors: Department of Neuropsychology, King Faisal Specialist Hospital and Research Centre, Riyadh, Saudi Arabia.
authors: Michael
authors: M
authors: Nester
authors: Department of Medical Genetics, AP-HP Robert DEBRE University Hospital and INSERM U676, Paris, France.
authors: Alain
authors: A
authors: Verloes
authors: Department of Medical Genetics, King Faisal Specialist Hospital and Research Centre, Riyadh, Saudi Arabia. Electronic address: hzaidan@kfshrc.edu.sa.
authors: Hamad
authors: H
authors: Al-Zaidan
mesh_terms: D000293:Adolescent; D061085:Agenesis of Corpus Callosum / Q000235:genetics* / Q000378:metabolism; D002648:Child; D002675:Child, Preschool; D018389:Codon, Nonsense; D004252:DNA Mutational Analysis; D005260:Female; D015870:Gene Expression; D006319:Hearing Loss, Sensorineural / Q000235:genetics* / Q000378:metabolism; D065630:Hernias, Diaphragmatic, Congenital / Q000235:genetics* / Q000378:metabolism; D006801:Humans; D007223:Infant; D007231:Infant, Newborn; D026561:Low Density Lipoprotein Receptor-Related Protein-2 / Q000235:genetics* / Q000378:metabolism; D008297:Male; D020125:Mutation, Missense; D009216:Myopia / Q000235:genetics* / Q000378:metabolism; D011507:Proteinuria / Q000235:genetics* / Q000378:metabolism; D015499:Renal Tubular Transport, Inborn Errors / Q000235:genetics* / Q000378:metabolism; D055815:Young Adult
chemical_list: D018389:Codon, Nonsense; C000597357:LRP2 protein, human; D026561:Low Density Lipoprotein Receptor-Related Protein-2
keywords: Agenesis of corpus callosum; Congenital diaphragmatic hernia; Donnai-Barrow syndrome; Hypertelorism; Omphalocele; Sensorineural hearing loss