RESUMO
PURPOSE: To describe a novel laminin ß-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 â 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 ß-2 chain. FINANCIAL DISCLOSURE(S): The author(s) have no proprietary or commercial interest in any materials discussed in this article.
Assuntos
DNA/genética , Predisposição Genética para Doença , Laminina/genética , Mutação de Sentido Incorreto , Anormalidades Múltiplas/genética , Anormalidades Múltiplas/metabolismo , Adolescente , Adulto , Idoso , Criança , Pré-Escolar , Cromossomos Humanos Par 3 , DNA/metabolismo , Análise Mutacional de DNA , Anormalidades do Olho/genética , Anormalidades do Olho/metabolismo , Feminino , Seguimentos , Humanos , Lactente , Laminina/metabolismo , Masculino , Pessoa de Meia-Idade , Síndromes Miastênicas Congênitas , Síndrome Nefrótica , Linhagem , Fenótipo , Distúrbios Pupilares/genética , Distúrbios Pupilares/metabolismo , Estudos Retrospectivos , Adulto JovemRESUMO
It is with deep sadness that I report news of the death of Peter Kavanagh, registrar at the Norfolk College of Nursing and Midwifery, Norwich.
