IQCB1 mutations in patients with leber congenital amaurosis

Alejandro Estrada-Cuzcano; Robert K Koenekoop; Frauke Coppieters; Susanne Kohl; Irma Lopez; Rob W J Collin; Elfride B W De Baere; Debbie Roeleveld; Jonah Marek; Antje Bernd; Klaus Rohrschneider; L Ingeborgh van den Born; Françoise Meire; Irene H Maumenee; Samuel G Jacobson; Carel B Hoyng; Eberhart Zrenner; Frans P M Cremers; Anneke I den Hollander

doi:10.1167/iovs.10-5221

IQCB1 mutations in patients with leber congenital amaurosis

Alejandro Estrada-Cuzcano, Robert K Koenekoop, Frauke Coppieters, Susanne Kohl, Irma Lopez, Rob W J Collin, Elfride B W De Baere, Debbie Roeleveld, Jonah Marek, Antje Bernd, Klaus Rohrschneider, L Ingeborgh van den Born, Françoise Meire, Irene H Maumenee, Samuel G Jacobson, Carel B Hoyng, Eberhart Zrenner, Frans P M Cremers, Anneke I den Hollander

Medical retina and Uveitis

Research output: Contribution to journal › Article › Research › peer-review

Abstract

PURPOSE: Leber congenital amaurosis (LCA) is genetically heterogeneous, with 15 genes identified thus far, accounting for ∼70% of LCA patients. The aim of the present study was to identify new genetic causes of LCA.

METHODS: Homozygosity mapping in >150 LCA patients of worldwide origin was performed with high-density SNP microarrays to identify new disease-causing genes.

RESULTS: In three isolated LCA patients, the authors identified large homozygous regions on chromosome 3 encompassing the IQCB1 gene, which has been associated with Senior-Loken syndrome (SLSN), characterized by nephronophthisis and retinal degeneration. Mutation analysis of IQCB1 in these three patients and a subsequent cohort of 222 additional LCA patients identified frameshift and nonsense mutations in 11 patients diagnosed with LCA. On re-inspection of the patient's disease status, seven were found to have developed SLSN, but four maintained the diagnosis of LCA as the kidney function remained normal.

CONCLUSIONS: Results show that the onset of renal failure in patients with IQCB1 mutations is highly variable, and that mutations are also found in LCA patients without nephronophthisis, rendering IQCB1 a new gene for LCA. However, these patients are at high risk for developing renal failure, which in early stages is often not recognized and can cause sudden death from fluid and electrolyte imbalance. It is therefore recommended that all LCA patients be screened for IQCB1 mutations, to follow them more closely for kidney disease.

Original language	English
Pages (from-to)	834-9
Number of pages	6
Journal	Investigative ophthalmology & visual science
Volume	52
Issue number	2
DOIs	https://doi.org/10.1167/iovs.10-5221
Publication status	Published - 11 Feb 2011

Keywords

Adolescent
Adult
Calmodulin-Binding Proteins/genetics
Child
Child, Preschool
Chromosomes, Human, Pair 3/genetics
Ciliopathies
Codon, Nonsense
DNA Mutational Analysis
Female
Frameshift Mutation
Genotype
Humans
Kidney Diseases, Cystic/genetics
Leber Congenital Amaurosis/diagnosis
Male
Middle Aged
Optic Atrophies, Hereditary/genetics
Polymerase Chain Reaction
Polymorphism, Single Nucleotide

Access to Document

10.1167/iovs.10-5221

Cite this

Estrada-Cuzcano, A., Koenekoop, R. K., Coppieters, F., Kohl, S., Lopez, I., Collin, R. W. J., De Baere, E. B. W., Roeleveld, D., Marek, J., Bernd, A., Rohrschneider, K., van den Born, L. I., Meire, F., Maumenee, I. H., Jacobson, S. G., Hoyng, C. B., Zrenner, E., Cremers, F. P. M., & den Hollander, A. I. (2011). IQCB1 mutations in patients with leber congenital amaurosis. Investigative ophthalmology & visual science, 52(2), 834-9. https://doi.org/10.1167/iovs.10-5221

@article{0df46e139ad24fb4a6fd871221ef2c67,

title = "IQCB1 mutations in patients with leber congenital amaurosis",

abstract = "PURPOSE: Leber congenital amaurosis (LCA) is genetically heterogeneous, with 15 genes identified thus far, accounting for ∼70% of LCA patients. The aim of the present study was to identify new genetic causes of LCA.METHODS: Homozygosity mapping in >150 LCA patients of worldwide origin was performed with high-density SNP microarrays to identify new disease-causing genes.RESULTS: In three isolated LCA patients, the authors identified large homozygous regions on chromosome 3 encompassing the IQCB1 gene, which has been associated with Senior-Loken syndrome (SLSN), characterized by nephronophthisis and retinal degeneration. Mutation analysis of IQCB1 in these three patients and a subsequent cohort of 222 additional LCA patients identified frameshift and nonsense mutations in 11 patients diagnosed with LCA. On re-inspection of the patient's disease status, seven were found to have developed SLSN, but four maintained the diagnosis of LCA as the kidney function remained normal.CONCLUSIONS: Results show that the onset of renal failure in patients with IQCB1 mutations is highly variable, and that mutations are also found in LCA patients without nephronophthisis, rendering IQCB1 a new gene for LCA. However, these patients are at high risk for developing renal failure, which in early stages is often not recognized and can cause sudden death from fluid and electrolyte imbalance. It is therefore recommended that all LCA patients be screened for IQCB1 mutations, to follow them more closely for kidney disease.",

keywords = "Adolescent, Adult, Calmodulin-Binding Proteins/genetics, Child, Child, Preschool, Chromosomes, Human, Pair 3/genetics, Ciliopathies, Codon, Nonsense, DNA Mutational Analysis, Female, Frameshift Mutation, Genotype, Humans, Kidney Diseases, Cystic/genetics, Leber Congenital Amaurosis/diagnosis, Male, Middle Aged, Optic Atrophies, Hereditary/genetics, Polymerase Chain Reaction, Polymorphism, Single Nucleotide",

author = "Alejandro Estrada-Cuzcano and Koenekoop, {Robert K} and Frauke Coppieters and Susanne Kohl and Irma Lopez and Collin, {Rob W J} and {De Baere}, {Elfride B W} and Debbie Roeleveld and Jonah Marek and Antje Bernd and Klaus Rohrschneider and {van den Born}, {L Ingeborgh} and Fran{\c c}oise Meire and Maumenee, {Irene H} and Jacobson, {Samuel G} and Hoyng, {Carel B} and Eberhart Zrenner and Cremers, {Frans P M} and {den Hollander}, {Anneke I}",

year = "2011",

month = feb,

day = "11",

doi = "10.1167/iovs.10-5221",

language = "English",

volume = "52",

pages = "834--9",

number = "2",

}

Estrada-Cuzcano, A, Koenekoop, RK, Coppieters, F, Kohl, S, Lopez, I, Collin, RWJ, De Baere, EBW, Roeleveld, D, Marek, J, Bernd, A, Rohrschneider, K, van den Born, LI, Meire, F, Maumenee, IH, Jacobson, SG, Hoyng, CB, Zrenner, E, Cremers, FPM & den Hollander, AI 2011, 'IQCB1 mutations in patients with leber congenital amaurosis', Investigative ophthalmology & visual science, vol. 52, no. 2, pp. 834-9. https://doi.org/10.1167/iovs.10-5221

TY - JOUR

T1 - IQCB1 mutations in patients with leber congenital amaurosis

AU - Estrada-Cuzcano, Alejandro

AU - Koenekoop, Robert K

AU - Coppieters, Frauke

AU - Kohl, Susanne

AU - Lopez, Irma

AU - Collin, Rob W J

AU - De Baere, Elfride B W

AU - Roeleveld, Debbie

AU - Marek, Jonah

AU - Bernd, Antje

AU - Rohrschneider, Klaus

AU - van den Born, L Ingeborgh

AU - Meire, Françoise

AU - Maumenee, Irene H

AU - Jacobson, Samuel G

AU - Hoyng, Carel B

AU - Zrenner, Eberhart

AU - Cremers, Frans P M

AU - den Hollander, Anneke I

PY - 2011/2/11

Y1 - 2011/2/11

N2 - PURPOSE: Leber congenital amaurosis (LCA) is genetically heterogeneous, with 15 genes identified thus far, accounting for ∼70% of LCA patients. The aim of the present study was to identify new genetic causes of LCA.METHODS: Homozygosity mapping in >150 LCA patients of worldwide origin was performed with high-density SNP microarrays to identify new disease-causing genes.RESULTS: In three isolated LCA patients, the authors identified large homozygous regions on chromosome 3 encompassing the IQCB1 gene, which has been associated with Senior-Loken syndrome (SLSN), characterized by nephronophthisis and retinal degeneration. Mutation analysis of IQCB1 in these three patients and a subsequent cohort of 222 additional LCA patients identified frameshift and nonsense mutations in 11 patients diagnosed with LCA. On re-inspection of the patient's disease status, seven were found to have developed SLSN, but four maintained the diagnosis of LCA as the kidney function remained normal.CONCLUSIONS: Results show that the onset of renal failure in patients with IQCB1 mutations is highly variable, and that mutations are also found in LCA patients without nephronophthisis, rendering IQCB1 a new gene for LCA. However, these patients are at high risk for developing renal failure, which in early stages is often not recognized and can cause sudden death from fluid and electrolyte imbalance. It is therefore recommended that all LCA patients be screened for IQCB1 mutations, to follow them more closely for kidney disease.

AB - PURPOSE: Leber congenital amaurosis (LCA) is genetically heterogeneous, with 15 genes identified thus far, accounting for ∼70% of LCA patients. The aim of the present study was to identify new genetic causes of LCA.METHODS: Homozygosity mapping in >150 LCA patients of worldwide origin was performed with high-density SNP microarrays to identify new disease-causing genes.RESULTS: In three isolated LCA patients, the authors identified large homozygous regions on chromosome 3 encompassing the IQCB1 gene, which has been associated with Senior-Loken syndrome (SLSN), characterized by nephronophthisis and retinal degeneration. Mutation analysis of IQCB1 in these three patients and a subsequent cohort of 222 additional LCA patients identified frameshift and nonsense mutations in 11 patients diagnosed with LCA. On re-inspection of the patient's disease status, seven were found to have developed SLSN, but four maintained the diagnosis of LCA as the kidney function remained normal.CONCLUSIONS: Results show that the onset of renal failure in patients with IQCB1 mutations is highly variable, and that mutations are also found in LCA patients without nephronophthisis, rendering IQCB1 a new gene for LCA. However, these patients are at high risk for developing renal failure, which in early stages is often not recognized and can cause sudden death from fluid and electrolyte imbalance. It is therefore recommended that all LCA patients be screened for IQCB1 mutations, to follow them more closely for kidney disease.

KW - Adolescent

KW - Adult

KW - Calmodulin-Binding Proteins/genetics

KW - Child

KW - Child, Preschool

KW - Chromosomes, Human, Pair 3/genetics

KW - Ciliopathies

KW - Codon, Nonsense

KW - DNA Mutational Analysis

KW - Female

KW - Frameshift Mutation

KW - Genotype

KW - Humans

KW - Kidney Diseases, Cystic/genetics

KW - Leber Congenital Amaurosis/diagnosis

KW - Male

KW - Middle Aged

KW - Optic Atrophies, Hereditary/genetics

KW - Polymerase Chain Reaction

KW - Polymorphism, Single Nucleotide

U2 - 10.1167/iovs.10-5221

DO - 10.1167/iovs.10-5221

M3 - Article

C2 - 20881296

SN - 0146-0404

VL - 52

SP - 834

EP - 839

JO - Investigative ophthalmology & visual science

JF - Investigative ophthalmology & visual science

IS - 2

ER -

IQCB1 mutations in patients with leber congenital amaurosis

Abstract

Keywords

Access to Document

Fingerprint

Cite this