Biallelic Mutations in the BEST1 Gene: Additional Families with Autosomal Recessive Bestrophinopathy

2015 ◽  
Vol 37 (2) ◽  
pp. 183-193 ◽  
Author(s):  
Ragnhild Wivestad Jansson ◽  
Siren Berland ◽  
Cecilie Bredrup ◽  
Dordi Austeng ◽  
Sten Andréasson ◽  
...  
Keyword(s):  
Autosomal Recessive ◽  
Autosomal Recessive Bestrophinopathy ◽  
Biallelic Mutations

scholarly journals Clinical and Genetic Findings of Autosomal Recessive Bestrophinopathy (ARB)

Genes ◽  
2019 ◽  
Vol 10 (12) ◽  
pp. 953 ◽  
Author(s):  
Imen Habibi ◽  
Yosra Falfoul ◽  
Margarita G. Todorova ◽  
Stefan Wyrsch ◽  
Veronika Vaclavik ◽  
...  
Keyword(s):  
Molecular Analysis ◽  
Autosomal Recessive ◽  
Novel Mutation ◽  
Macular Dystrophy ◽  
Phenotype Correlation ◽  
Corrected Visual Acuity ◽  
Light Rise ◽  
Autosomal Recessive Bestrophinopathy ◽  
Biallelic Mutations

Mutations in BEST1 cause several phenotypes including autosomal dominant (AD) Best vitelliform macular dystrophy type 2 (BVMD), AD vitreo-retino-choroidopathy (ADVIRC), and retinitis pigmentosa-50 (RP50). A rare subtype of Bestrophinopathy exists with biallelic mutations in BEST1. Its frequency is estimated to be 1/1,000,000 individuals. Here we report 6 families and searched for a genotype-phenotype correlation. All patients were referred due to reduced best-corrected visual acuity (BCVA), ranging from 0.1/10 to 3/10. They all showed vitelliform lesions located at the macula, sometimes extending into the midperiphery, along the vessels and the optic disc. Onset of the disease varied from the age of 3 to 25 years. Electrooculogram (EOG) revealed reduction in the EOG light rise in all patients. Molecular analysis revealed previously reported mutations p.(E35K);(E35K), p.(L31M);(L31M), p.(R141H);(A195V), p.(R202W);(R202W), and p.(Q220*);(Q220*) in five families. One family showed a novel mutation: p.(E167G);(E167G). All mutations were heterozygous in the parents. In one family, heterozygous children showed various reductions in the EOG light rise and autofluorescent deposits. Autosomal recessive Bestrophinopathy (ARB), although rare, can be recognized by its phenotype and should be validated by molecular analysis. Genotype-phenotype correlations are difficult to establish and will require the analysis of additional cases.

scholarly journals Clinical Heterogeneity in Autosomal Recessive Bestrophinopathy with Biallelic Mutations in the BEST1 Gene

2020 ◽  
Vol 21 (24) ◽  
pp. 9353
Author(s):  
Karsten Hufendiek ◽  
Katerina Hufendiek ◽  
Herbert Jägle ◽  
Heidi Stöhr ◽  
Marius Book ◽  
...  
Keyword(s):  
Autosomal Recessive ◽  
Age Of Onset ◽  
Fundus Autofluorescence ◽  
Serous Retinal Detachment ◽  
Fundus Photography ◽  
Macular Dystrophy ◽  
Ophthalmological Examination ◽  
Hyperreflective Foci ◽  
Autosomal Recessive Bestrophinopathy ◽  
Biallelic Mutations

Autosomal recessive bestrophinopathy (ARB) has been reported as clinically heterogeneous. Eighteen patients (mean age: 22.5 years; 15 unrelated families) underwent ophthalmological examination, fundus photography, fundus autofluorescence, and optical coherence tomography (OCT). Molecular genetic testing of the BEST1 gene was conducted by the chain-terminating dideoxynucleotide Sanger methodology. Onset of symptoms (3 to 50 years of age) and best-corrected visual acuity (0.02–1.0) were highly variable. Ophthalmoscopic and retinal imaging defined five phenotypes. Phenotype I presented with single or confluent yellow lesions at the posterior pole and midperiphery, serous retinal detachment, and intraretinal cystoid spaces. In phenotype II fleck-like lesions were smaller and extended to the far periphery. Phenotype III showed a widespread continuous lesion with sharp peripheral demarcation. Single (phenotype IV) or multifocal (phenotype V) vitelliform macular dystrophy-like lesions were observed as well. Phenotypes varied within families and in two eyes of one patient. In addition, OCT detected hyperreflective foci (13/36 eyes) and choroidal excavation (11/36). Biallelic mutations were identified in each patient, six of which have not been reported so far [c.454C>T/p.(Pro152Ser), c.620T>A/p.(Leu207His), c.287_298del/p.(Gln96_Asn99del), c.199_200del/p.(Leu67Valfs*164), c.524del/p.(Ser175Thrfs*19), c.590_615del/p.(Leu197Profs*26)]. BEST1-associated ARB presents with a variable age of onset and clinical findings, that can be categorized in 5 clinical phenotypes. Hyperreflective foci and choroidal excavation frequently develop as secondary manifestations.

scholarly journals The Sodium-Iodide Symporter NIS and Pendrin in Iodide Homeostasis of the Thyroid

Endocrinology ◽  
2009 ◽  
Vol 150 (3) ◽  
pp. 1084-1090 ◽  
Author(s):  
Aigerim Bizhanova ◽  
Peter Kopp
Keyword(s):  
Autosomal Recessive ◽  
Sodium Iodide ◽  
Basolateral Membrane ◽  
Sensorineural Deafness ◽  
Sodium Iodide Symporter ◽  
Pendred Syndrome ◽  
Iodide Uptake ◽  
Anion Transporter ◽  
Thyroid Hormone Biosynthesis ◽  
Biallelic Mutations

Thyroid hormones are essential for normal development and metabolism. Thyroid hormone biosynthesis requires iodide uptake into the thyrocytes and efflux into the follicular lumen, where it is organified on selected tyrosyls of thyroglobulin. Uptake of iodide into the thyrocytes is mediated by an intrinsic membrane glycoprotein, the sodium-iodide symporter (NIS), which actively cotransports two sodium cations per each iodide anion. NIS-mediated transport of iodide is driven by the electrochemical sodium gradient generated by the Na+/K+-ATPase. NIS is expressed in the thyroid, the salivary glands, gastric mucosa, and the lactating mammary gland. TSH and iodide regulate iodide accumulation by modulating NIS activity via transcriptional and posttranscriptional mechanisms. Biallelic mutations in the NIS gene lead to a congenital iodide transport defect, an autosomal recessive condition characterized by hypothyroidism, goiter, low thyroid iodide uptake, and a low saliva/plasma iodide ratio. Pendrin is an anion transporter that is predominantly expressed in the inner ear, the thyroid, and the kidney. Biallelic mutations in the SLC26A4 gene lead to Pendred syndrome, an autosomal recessive disorder characterized by sensorineural deafness, goiter, and impaired iodide organification. In thyroid follicular cells, pendrin is expressed at the apical membrane. Functional in vitro data and the impaired iodide organification observed in patients with Pendred syndrome support a role of pendrin as an apical iodide transporter. This review shows how the sodium-iodide symporter mediates the active transport of iodide at the basolateral membrane of thyrocytes and discusses biallelic mutations in NIS and the effects of pendrin.

scholarly journals Unexpected Genetic Cause in Two Female Siblings with High Myopia and Reduced Visual Acuity

2018 ◽  
Vol 2018 ◽  
pp. 1-11 ◽  
Author(s):  
M. N. Preising ◽  
C. Friedburg ◽  
W. Bowl ◽  
B. Lorenz
Keyword(s):  
Visual Acuity ◽  
High Myopia ◽  
Autosomal Recessive ◽  
Electrical Coupling ◽  
Splice Site Mutation ◽  
Bipolar Cells ◽  
Night Vision ◽  
Site Mutation ◽  
Frequent Finding ◽  
Biallelic Mutations

In daily life, myopia is a frequent cause of reduced visual acuity (VA) due to missing or incomplete optical correction. While the genetic cause of high myopia itself is not well understood, a significant number of cases are secondary to hereditary malfunctions or degenerations of the retina. The mechanism by which this occurs remains yet unclear. Two female siblings, 4 y and 2 y, respectively, from a consanguineous Pakistani family were referred to our department for reduced VA and strabismus. Both girls were highly myopic and hence were further examined using standard clinical tests and electroretinography (ERG). The latter confirmed confounded electrical coupling of photoreceptors and bipolar cells. Further inquiry and testing confirmed a similar condition for the father including impaired night vision, reduced VA, photophobia, and an equally characteristic ERG. Findings in the mother were unremarkable. Subsequent genetic analysis of autosomal recessive and X-linked genes for congenital stationary night blindness (CSNB) revealed a novel homozygous splice site mutation in CACNA1F in the two girls transmitted from both the father and the mother. While in males the above clinical constellation is a frequent finding, this report, to the authors’ knowledge, is the first demonstrating biallelic mutations at the CACNA1F locus in females.

scholarly journals Mutant Best1 Expression and Impaired Phagocytosis in an iPSC Model of Autosomal Recessive Bestrophinopathy

2018 ◽  
Vol 8 (1) ◽  
Author(s):  
Alan D. Marmorstein ◽  
Adiv A. Johnson ◽  
Lori A. Bachman ◽  
Cynthia Andrews-Pfannkoch ◽  
Travis Knudsen ◽  
...  
Keyword(s):  
Autosomal Recessive ◽  
Autosomal Recessive Bestrophinopathy

Biallelic mutations in the LPAR 6 gene causing autosomal recessive wooly hair/hypotrichosis phenotype in five Pakistani families

2019 ◽  
Vol 58 (8) ◽  
pp. 946-952 ◽  
Author(s):  
Ghulam M. Khan ◽  
Noor Hassan ◽  
Niamatullah Khan ◽  
Muhammad Humayun ◽  
Kafaitullah Khan ◽  
...  
Keyword(s):  
Autosomal Recessive ◽  
Biallelic Mutations ◽  
Pakistani Families

scholarly journals Case Report: Expanding the Genetic and Phenotypic Spectrum of Autosomal Recessive Spastic Ataxia of Charlevoix-Saguenay

2020 ◽  
Vol 11 ◽  
Author(s):  
Parham Habibzadeh ◽  
Zahra Tabatabaei ◽  
Soroor Inaloo ◽  
Muhammad Mahdi Nashatizadeh ◽  
Matthis Synofzik ◽  
...  
Keyword(s):  
Case Report ◽  
Clinical Features ◽  
Autosomal Recessive ◽  
Neurodegenerative Disorder ◽  
Deletion Mutation ◽  
Sensorimotor Neuropathy ◽  
Spastic Ataxia ◽  
Phenotypic Spectrum ◽  
Iranian Family ◽  
Biallelic Mutations

Autosomal recessive spastic ataxia of Charlevoix–Saguenay (ARSACS) is a rare neurodegenerative disorder caused by biallelic mutations in the SACS gene. Once thought to be limited to Charlevoix–Saguenay region of Quebec, recent evidence has indicated that this disorder is present worldwide. It is classically characterized by the triad of ataxia, pyramidal involvement, and axonal-demyelinating sensorimotor neuropathy. However, diverse clinical features have been reported to be associated with this disorder. In this report, we present the first Iranian family affected by ARSACS with unique clinical features (mirror movements, hypokinesia/bradykinesia, and rigidity) harboring a novel deletion mutation in the SACS gene. Our findings expand the genetic and phenotypic spectrum of this disorder.

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