A novel mutation of LAMB2 in a multigenerational mennonite family reveals a new phenotypic variant of Pierson syndrome

Brian G. Mohney, Jose S Pulido, Noralane Morey Lindor, Marie C Hogan, Mark B. Consugar, Justin Peters, V. Shane Pankratz, Samih H. Nasr, Stephen J. Smith, James Gloor, Vickie Kubly, Dorothy Spencer, Rebecca Nielson, Erik G. Puffenberger, Kevin A. Strauss, D. Holmes Morton, Lama Eldahdah, Peter C Harris

Research output: Contribution to journalArticle

18 Citations (Scopus)

Abstract

Purpose To describe a novel laminin β-2 (LAMB2) mutation associated with nephrotic syndrome and severe retinal disease without microcoria in a large, multigenerational family with Pierson syndrome. Design Retrospective chart review and prospective family examination. Participants An extended consanguineous family of 52 members. Methods The eyes, urine, and serum DNA were evaluated in all family members after discovering 2 patients, both younger than 10 years, with bilateral retinal detachments and concurrent renal dysfunction. Linkage analysis was performed in the 9 living affected individuals, 7 using the Illumina Human Hap370 Duo Bead Array (Illumina, San Diego, CA) and 2 using GeneChip 10K (Affymetrix, Santa Clara, CA) mapping arrays. Main Outcome Measures The prevalence and severity of ocular and kidney involvement and genetic findings. Results Eleven affected family members were identified (9 living), all manifesting chronic kidney disease and bilateral chorioretinal pigmentary changes, with or without retinal detachments, but without microcoria or neurodevelopmental deficits, segregating in an autosomal recessive pattern. The causative gene was localized to a 9-Mb region on chromosome 3. Comprehensive gene sequencing revealed a novel LAMB2 variant (c.440A→G; His147R) that was homozygous in the 9 living, affected family members, observed at a frequency of 2.1% in the Old Order Mennonite population, and absent in 91 non-Mennonite controls. The mutation is located in a highly conserved site in the N-terminal domain VI of LAMB2. Conclusions This study describes a novel mutation of LAMB2 and further expands the spectrum of eye and renal manifestations associated with defects in the laminin β-2 chain. Financial Disclosure(s) The author(s) have no proprietary or commercial interest in any materials discussed in this article.

Original languageEnglish (US)
Pages (from-to)1137-1144
Number of pages8
JournalOphthalmology
Volume118
Issue number6
DOIs
StatePublished - Jun 2011

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Mutation
Laminin
Retinal Detachment
Kidney
Eye Manifestations
Retinal Diseases
Chromosomes, Human, Pair 3
Disclosure
Nephrotic Syndrome
Pierson syndrome
Chronic Renal Insufficiency
Genes
Outcome Assessment (Health Care)
Urine
DNA
Serum
Population

ASJC Scopus subject areas

  • Ophthalmology

Cite this

A novel mutation of LAMB2 in a multigenerational mennonite family reveals a new phenotypic variant of Pierson syndrome. / Mohney, Brian G.; Pulido, Jose S; Lindor, Noralane Morey; Hogan, Marie C; Consugar, Mark B.; Peters, Justin; Pankratz, V. Shane; Nasr, Samih H.; Smith, Stephen J.; Gloor, James; Kubly, Vickie; Spencer, Dorothy; Nielson, Rebecca; Puffenberger, Erik G.; Strauss, Kevin A.; Morton, D. Holmes; Eldahdah, Lama; Harris, Peter C.

In: Ophthalmology, Vol. 118, No. 6, 06.2011, p. 1137-1144.

Research output: Contribution to journalArticle

Mohney, BG, Pulido, JS, Lindor, NM, Hogan, MC, Consugar, MB, Peters, J, Pankratz, VS, Nasr, SH, Smith, SJ, Gloor, J, Kubly, V, Spencer, D, Nielson, R, Puffenberger, EG, Strauss, KA, Morton, DH, Eldahdah, L & Harris, PC 2011, 'A novel mutation of LAMB2 in a multigenerational mennonite family reveals a new phenotypic variant of Pierson syndrome', Ophthalmology, vol. 118, no. 6, pp. 1137-1144. https://doi.org/10.1016/j.ophtha.2010.10.009
Mohney, Brian G. ; Pulido, Jose S ; Lindor, Noralane Morey ; Hogan, Marie C ; Consugar, Mark B. ; Peters, Justin ; Pankratz, V. Shane ; Nasr, Samih H. ; Smith, Stephen J. ; Gloor, James ; Kubly, Vickie ; Spencer, Dorothy ; Nielson, Rebecca ; Puffenberger, Erik G. ; Strauss, Kevin A. ; Morton, D. Holmes ; Eldahdah, Lama ; Harris, Peter C. / A novel mutation of LAMB2 in a multigenerational mennonite family reveals a new phenotypic variant of Pierson syndrome. In: Ophthalmology. 2011 ; Vol. 118, No. 6. pp. 1137-1144.
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abstract = "Purpose To describe a novel laminin β-2 (LAMB2) mutation associated with nephrotic syndrome and severe retinal disease without microcoria in a large, multigenerational family with Pierson syndrome. Design Retrospective chart review and prospective family examination. Participants An extended consanguineous family of 52 members. Methods The eyes, urine, and serum DNA were evaluated in all family members after discovering 2 patients, both younger than 10 years, with bilateral retinal detachments and concurrent renal dysfunction. Linkage analysis was performed in the 9 living affected individuals, 7 using the Illumina Human Hap370 Duo Bead Array (Illumina, San Diego, CA) and 2 using GeneChip 10K (Affymetrix, Santa Clara, CA) mapping arrays. Main Outcome Measures The prevalence and severity of ocular and kidney involvement and genetic findings. Results Eleven affected family members were identified (9 living), all manifesting chronic kidney disease and bilateral chorioretinal pigmentary changes, with or without retinal detachments, but without microcoria or neurodevelopmental deficits, segregating in an autosomal recessive pattern. The causative gene was localized to a 9-Mb region on chromosome 3. Comprehensive gene sequencing revealed a novel LAMB2 variant (c.440A→G; His147R) that was homozygous in the 9 living, affected family members, observed at a frequency of 2.1{\%} in the Old Order Mennonite population, and absent in 91 non-Mennonite controls. The mutation is located in a highly conserved site in the N-terminal domain VI of LAMB2. Conclusions This study describes a novel mutation of LAMB2 and further expands the spectrum of eye and renal manifestations associated with defects in the laminin β-2 chain. Financial Disclosure(s) The author(s) have no proprietary or commercial interest in any materials discussed in this article.",
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AU - Mohney, Brian G.

AU - Pulido, Jose S

AU - Lindor, Noralane Morey

AU - Hogan, Marie C

AU - Consugar, Mark B.

AU - Peters, Justin

AU - Pankratz, V. Shane

AU - Nasr, Samih H.

AU - Smith, Stephen J.

AU - Gloor, James

AU - Kubly, Vickie

AU - Spencer, Dorothy

AU - Nielson, Rebecca

AU - Puffenberger, Erik G.

AU - Strauss, Kevin A.

AU - Morton, D. Holmes

AU - Eldahdah, Lama

AU - Harris, Peter C

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N2 - Purpose To describe a novel laminin β-2 (LAMB2) mutation associated with nephrotic syndrome and severe retinal disease without microcoria in a large, multigenerational family with Pierson syndrome. Design Retrospective chart review and prospective family examination. Participants An extended consanguineous family of 52 members. Methods The eyes, urine, and serum DNA were evaluated in all family members after discovering 2 patients, both younger than 10 years, with bilateral retinal detachments and concurrent renal dysfunction. Linkage analysis was performed in the 9 living affected individuals, 7 using the Illumina Human Hap370 Duo Bead Array (Illumina, San Diego, CA) and 2 using GeneChip 10K (Affymetrix, Santa Clara, CA) mapping arrays. Main Outcome Measures The prevalence and severity of ocular and kidney involvement and genetic findings. Results Eleven affected family members were identified (9 living), all manifesting chronic kidney disease and bilateral chorioretinal pigmentary changes, with or without retinal detachments, but without microcoria or neurodevelopmental deficits, segregating in an autosomal recessive pattern. The causative gene was localized to a 9-Mb region on chromosome 3. Comprehensive gene sequencing revealed a novel LAMB2 variant (c.440A→G; His147R) that was homozygous in the 9 living, affected family members, observed at a frequency of 2.1% in the Old Order Mennonite population, and absent in 91 non-Mennonite controls. The mutation is located in a highly conserved site in the N-terminal domain VI of LAMB2. Conclusions This study describes a novel mutation of LAMB2 and further expands the spectrum of eye and renal manifestations associated with defects in the laminin β-2 chain. Financial Disclosure(s) The author(s) have no proprietary or commercial interest in any materials discussed in this article.

AB - Purpose To describe a novel laminin β-2 (LAMB2) mutation associated with nephrotic syndrome and severe retinal disease without microcoria in a large, multigenerational family with Pierson syndrome. Design Retrospective chart review and prospective family examination. Participants An extended consanguineous family of 52 members. Methods The eyes, urine, and serum DNA were evaluated in all family members after discovering 2 patients, both younger than 10 years, with bilateral retinal detachments and concurrent renal dysfunction. Linkage analysis was performed in the 9 living affected individuals, 7 using the Illumina Human Hap370 Duo Bead Array (Illumina, San Diego, CA) and 2 using GeneChip 10K (Affymetrix, Santa Clara, CA) mapping arrays. Main Outcome Measures The prevalence and severity of ocular and kidney involvement and genetic findings. Results Eleven affected family members were identified (9 living), all manifesting chronic kidney disease and bilateral chorioretinal pigmentary changes, with or without retinal detachments, but without microcoria or neurodevelopmental deficits, segregating in an autosomal recessive pattern. The causative gene was localized to a 9-Mb region on chromosome 3. Comprehensive gene sequencing revealed a novel LAMB2 variant (c.440A→G; His147R) that was homozygous in the 9 living, affected family members, observed at a frequency of 2.1% in the Old Order Mennonite population, and absent in 91 non-Mennonite controls. The mutation is located in a highly conserved site in the N-terminal domain VI of LAMB2. Conclusions This study describes a novel mutation of LAMB2 and further expands the spectrum of eye and renal manifestations associated with defects in the laminin β-2 chain. Financial Disclosure(s) The author(s) have no proprietary or commercial interest in any materials discussed in this article.

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