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

Khalifa, Ola; Alsahlawi, Zahra; Imtiaz, Faiqa; Ramzan, Khushnooda; Allam, Rabab; Al-Mostafa, Abeer; Abdel-Fattah, Maaly; Abuharb, Gheid; Nester, Michael; Verloès, Alain; Alzaidan, Hamad

doi:10.1016/j.ejmg.2014.12.008

Cited by 40 publications

(29 citation statements)

References 26 publications

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“…The rare, autosomal recessive disorder Donnai-Barrow facio-oculo-acousticorenal syndrome (DBS/FOAR) (OMIM 222448) is caused by mutations in the LRP2 gene. 69 Only about 30 cases have been published, 70,71 and the syndrome is characterized by a distinct facial appearance, including hypertelorism, along with functional defects such as high-grade myopia, sensorineural hearing loss, developmental delay, and in some cases agenesis of the corpus callosum, congenital diaphragmatic hernia, and omphalocele or umbilical hernia. Proteinuria has been reported in all patients in whom this was analyzed.…”

Section: Megalin and Cubilin Dysfunction In Humansmentioning

confidence: 99%

Megalin and cubilin in proximal tubule protein reabsorption: from experimental models to human disease

Nielsen

Christensen

Birn

2016

Kidney International

361

298

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Proximal tubule protein uptake is mediated by 2 receptors, megalin and cubilin. These receptors rescue a variety of filtered ligands, including biomarkers, essential vitamins, and hormones. Receptor gene knockout animal models have identified important functions of the receptors and have established their essential role in modulating urinary protein excretion. Rare genetic syndromes associated with dysfunction of these receptors have been identified and characterized, providing additional information on the importance of these receptors in humans. Using various disease models in combination with receptor gene knockout, the implications of receptor dysfunction in acute and chronic kidney injury have been explored and have pointed to potential new roles of these receptors. Based on data from animal models, this paper will review current knowledge on proximal tubule endocytic receptor function and regulation, and their role in renal development, protein reabsorption, albumin uptake, and normal renal physiology. These findings have implications for the pathophysiology and diagnosis of proteinuric renal diseases. We will examine the limitations of the different models and compare the findings to phenotypic observations in inherited human disorders associated with receptor dysfunction. Furthermore, evidence from receptor knockout mouse models as well as human observations suggesting a role of protein receptors for renal disease will be discussed in light of conditions such as chronic kidney disease, diabetes, and hypertension.

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Section: Megalin and Cubilin Dysfunction In Humansmentioning

confidence: 99%

Megalin and cubilin in proximal tubule protein reabsorption: from experimental models to human disease

Nielsen

Christensen

Birn

2016

Kidney International

361

298

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“…We identify a subset of deafness genes that are expressed in adult SV cell types. Deafness genes expressed in marginal cells include Lrp2, Esrrb, Hgf, Kcnq1, Kcne1, Ror1, and Eya4 (Wayne, 2001;Wangemann, 2002;Zhang et al, 2004;Collin et al, 2008;König et al, 2008;Schultz et al, 2009;Khalifa et al, 2015;Faridi et al, 2019). Deafness genes expressed in intermediate cells include Met, Pde1c, and Pax3 (Tassabehji et al, 1993;Bondurand, 2000;Mujtaba et al, 2015;Wang et al, 2018).…”

Section: Deafness Gene Mapping Suggests a Role For Sv Cell Types In Hmentioning

confidence: 99%

Single Cell and Single Nucleus RNA-Seq Reveal Cellular Heterogeneity and Homeostatic Regulatory Networks in Adult Mouse Stria Vascularis

Korrapati

Taukulis

Olszewski

et al. 2019

Front. Mol. Neurosci.

128

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The stria vascularis (SV) generates the endocochlear potential (EP) in the inner ear and is necessary for proper hair cell mechanotransduction and hearing. While channels belonging to SV cell types are known to play crucial roles in EP generation, relatively little is known about gene regulatory networks that underlie the ability of the SV to generate and maintain the EP. Using single cell and single nucleus RNA-sequencing, we identify and validate known and rare cell populations in the SV. Furthermore, we establish a basis for understanding molecular mechanisms underlying SV function by identifying potential gene regulatory networks as well as druggable gene targets. Finally, we associate known deafness genes with adult SV cell types. This work establishes a basis for dissecting the genetic mechanisms underlying the role of the SV in hearing and will serve as a basis for designing therapeutic approaches to hearing loss related to SV dysfunction.

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“…The identification of LRP2 mutations as cause of the autosomal recessive disorder DBS confirmed the relevance of LRP2 for the development of forebrain and facial structures in humans (Kantarci et al, ; Kantarci et al, ; Rosenfeld et al, ). DBS is a facio‐oculo‐acoustico‐renal syndrome that also includes microforms of HPE (Khalifa et al, ). All known LRP2 mutations affect the extracellular domain of the receptor polypeptide, in most instances causing expression of a truncated soluble receptor ectodomain.…”

Section: Lrp2 An Endocytic Receptor Directing Ligands Into Differentmentioning

confidence: 99%

LRP2, an auxiliary receptor that controls sonic hedgehog signaling in development and disease

Christ

Herzog

Willnow

2016

Developmental Dynamics

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To fulfill their multiple roles in organ development and adult tissue homeostasis, hedgehog (HH) morphogens act through their receptor Patched (PTCH) on target cells. However, HH actions also require HH binding proteins, auxiliary cell surface receptors that agonize or antagonize morphogen signaling in a context-dependent manner. Here, we discuss recent findings on the LDL receptor-related protein 2 (LRP2), an exemplary HH binding protein that modulates sonic hedgehog activities in stem and progenitor cell niches in embryonic and adult tissues. LRP2 functions are crucial for developmental processes in a number of tissues, including the brain, the eye, and the heart, and defects in this receptor pathway are the cause of devastating congenital diseases in humans. Developmental Dynamics 245:569-579,

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

Cited by 40 publications

References 26 publications

Megalin and cubilin in proximal tubule protein reabsorption: from experimental models to human disease

Megalin and cubilin in proximal tubule protein reabsorption: from experimental models to human disease

Single Cell and Single Nucleus RNA-Seq Reveal Cellular Heterogeneity and Homeostatic Regulatory Networks in Adult Mouse Stria Vascularis

LRP2, an auxiliary receptor that controls sonic hedgehog signaling in development and disease

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