Analysis of the OA1 gene reveals mutations in only one-third of patients with X-linked ocular albinism

M. Vittoria Schiaffino, Maria T. Bassi, Lucia Galli, Alessandra Renieri, Mirella Bruttini, Filomena De Nigris, Arthur A B Bergen, Stephen J. Charles, John R W Yates, Alfons Meindl, Richard A. Lewis, Richard A. King, Andrea Ballabio

Research output: Contribution to journalArticle

74 Citations (Scopus)

Abstract

The locus for ocular albinism type 1 (OA1) has been assigned to the Xp22.3 region through both linkage and deletion mapping. The disorder was found to be genetically homogeneous, as all informative families showed convincing linkage data with markers on Xp22.3 and all identified deletions involved the same region. The OA1 gene was recently cloned and several intragenic deletions were identified in affected individuals. We have characterized the genomic structure of the OA1 gene, which spans approximately 40 kb of genomic DNA and contains nine exons. A highly polymorphic dinucleotide repeat was identified in intron 1, that provides a useful tool for molecular diagnosis. Knowledge of the intron/exon boundaries allowed us to search for point mutations in patients' genomic DNA. All nine exons of the OA1 gene, as well as the 5′ and 3′ untranslated regions, were scanned for point mutations in PCR-amplified DNA from 60 OA1 patients. The mutations identified include: two frameshifts and a splice site mutation leading to truncated OA1 proteins; a deletion of a threonine codon at position 290; and four missense mutations, two of which involve amino acids located within putative transmembrane domains. Two of the mutations each occur in three apparently unrelated families, consistent with previous observations of a founder effect in OA1. Surprisingly, mutations were detected in only one-third of the patients (21 of 60) ascertained. We postulate that mutations not yet identified in either regulatory elements of the OA1 gene, or in other gene(s) located within the same chromosomal region, may be a common cause of X-linked ocular albinism.

Original languageEnglish
Pages (from-to)2319-2325
Number of pages7
JournalHuman Molecular Genetics
Volume4
Issue number12
DOIs
Publication statusPublished - Dec 1995

Fingerprint

Ocular Albinism
Mutation
Genes
Gene
DNA
Deletion
Genomics
Exons
Point Mutation
Linkage
Introns
Amino acids
Dinucleotide Repeats
Founder Effect
Ocular Albinism type 1
Chromosome Mapping
5' Untranslated Regions
Information Storage and Retrieval
3' Untranslated Regions
Proteins

ASJC Scopus subject areas

  • Statistics, Probability and Uncertainty
  • Applied Mathematics
  • Public Health, Environmental and Occupational Health
  • Molecular Biology
  • Genetics(clinical)
  • Genetics

Cite this

Analysis of the OA1 gene reveals mutations in only one-third of patients with X-linked ocular albinism. / Schiaffino, M. Vittoria; Bassi, Maria T.; Galli, Lucia; Renieri, Alessandra; Bruttini, Mirella; Nigris, Filomena De; Bergen, Arthur A B; Charles, Stephen J.; Yates, John R W; Meindl, Alfons; Lewis, Richard A.; King, Richard A.; Ballabio, Andrea.

In: Human Molecular Genetics, Vol. 4, No. 12, 12.1995, p. 2319-2325.

Research output: Contribution to journalArticle

Schiaffino, MV, Bassi, MT, Galli, L, Renieri, A, Bruttini, M, Nigris, FD, Bergen, AAB, Charles, SJ, Yates, JRW, Meindl, A, Lewis, RA, King, RA & Ballabio, A 1995, 'Analysis of the OA1 gene reveals mutations in only one-third of patients with X-linked ocular albinism', Human Molecular Genetics, vol. 4, no. 12, pp. 2319-2325. https://doi.org/10.1093/hmg/4.12.2319
Schiaffino, M. Vittoria ; Bassi, Maria T. ; Galli, Lucia ; Renieri, Alessandra ; Bruttini, Mirella ; Nigris, Filomena De ; Bergen, Arthur A B ; Charles, Stephen J. ; Yates, John R W ; Meindl, Alfons ; Lewis, Richard A. ; King, Richard A. ; Ballabio, Andrea. / Analysis of the OA1 gene reveals mutations in only one-third of patients with X-linked ocular albinism. In: Human Molecular Genetics. 1995 ; Vol. 4, No. 12. pp. 2319-2325.
@article{13fee55ed2cd447ea556ab28e60536d2,
title = "Analysis of the OA1 gene reveals mutations in only one-third of patients with X-linked ocular albinism",
abstract = "The locus for ocular albinism type 1 (OA1) has been assigned to the Xp22.3 region through both linkage and deletion mapping. The disorder was found to be genetically homogeneous, as all informative families showed convincing linkage data with markers on Xp22.3 and all identified deletions involved the same region. The OA1 gene was recently cloned and several intragenic deletions were identified in affected individuals. We have characterized the genomic structure of the OA1 gene, which spans approximately 40 kb of genomic DNA and contains nine exons. A highly polymorphic dinucleotide repeat was identified in intron 1, that provides a useful tool for molecular diagnosis. Knowledge of the intron/exon boundaries allowed us to search for point mutations in patients' genomic DNA. All nine exons of the OA1 gene, as well as the 5′ and 3′ untranslated regions, were scanned for point mutations in PCR-amplified DNA from 60 OA1 patients. The mutations identified include: two frameshifts and a splice site mutation leading to truncated OA1 proteins; a deletion of a threonine codon at position 290; and four missense mutations, two of which involve amino acids located within putative transmembrane domains. Two of the mutations each occur in three apparently unrelated families, consistent with previous observations of a founder effect in OA1. Surprisingly, mutations were detected in only one-third of the patients (21 of 60) ascertained. We postulate that mutations not yet identified in either regulatory elements of the OA1 gene, or in other gene(s) located within the same chromosomal region, may be a common cause of X-linked ocular albinism.",
author = "Schiaffino, {M. Vittoria} and Bassi, {Maria T.} and Lucia Galli and Alessandra Renieri and Mirella Bruttini and Nigris, {Filomena De} and Bergen, {Arthur A B} and Charles, {Stephen J.} and Yates, {John R W} and Alfons Meindl and Lewis, {Richard A.} and King, {Richard A.} and Andrea Ballabio",
year = "1995",
month = "12",
doi = "10.1093/hmg/4.12.2319",
language = "English",
volume = "4",
pages = "2319--2325",
journal = "Human Molecular Genetics",
issn = "0964-6906",
publisher = "Oxford University Press",
number = "12",

}

TY - JOUR

T1 - Analysis of the OA1 gene reveals mutations in only one-third of patients with X-linked ocular albinism

AU - Schiaffino, M. Vittoria

AU - Bassi, Maria T.

AU - Galli, Lucia

AU - Renieri, Alessandra

AU - Bruttini, Mirella

AU - Nigris, Filomena De

AU - Bergen, Arthur A B

AU - Charles, Stephen J.

AU - Yates, John R W

AU - Meindl, Alfons

AU - Lewis, Richard A.

AU - King, Richard A.

AU - Ballabio, Andrea

PY - 1995/12

Y1 - 1995/12

N2 - The locus for ocular albinism type 1 (OA1) has been assigned to the Xp22.3 region through both linkage and deletion mapping. The disorder was found to be genetically homogeneous, as all informative families showed convincing linkage data with markers on Xp22.3 and all identified deletions involved the same region. The OA1 gene was recently cloned and several intragenic deletions were identified in affected individuals. We have characterized the genomic structure of the OA1 gene, which spans approximately 40 kb of genomic DNA and contains nine exons. A highly polymorphic dinucleotide repeat was identified in intron 1, that provides a useful tool for molecular diagnosis. Knowledge of the intron/exon boundaries allowed us to search for point mutations in patients' genomic DNA. All nine exons of the OA1 gene, as well as the 5′ and 3′ untranslated regions, were scanned for point mutations in PCR-amplified DNA from 60 OA1 patients. The mutations identified include: two frameshifts and a splice site mutation leading to truncated OA1 proteins; a deletion of a threonine codon at position 290; and four missense mutations, two of which involve amino acids located within putative transmembrane domains. Two of the mutations each occur in three apparently unrelated families, consistent with previous observations of a founder effect in OA1. Surprisingly, mutations were detected in only one-third of the patients (21 of 60) ascertained. We postulate that mutations not yet identified in either regulatory elements of the OA1 gene, or in other gene(s) located within the same chromosomal region, may be a common cause of X-linked ocular albinism.

AB - The locus for ocular albinism type 1 (OA1) has been assigned to the Xp22.3 region through both linkage and deletion mapping. The disorder was found to be genetically homogeneous, as all informative families showed convincing linkage data with markers on Xp22.3 and all identified deletions involved the same region. The OA1 gene was recently cloned and several intragenic deletions were identified in affected individuals. We have characterized the genomic structure of the OA1 gene, which spans approximately 40 kb of genomic DNA and contains nine exons. A highly polymorphic dinucleotide repeat was identified in intron 1, that provides a useful tool for molecular diagnosis. Knowledge of the intron/exon boundaries allowed us to search for point mutations in patients' genomic DNA. All nine exons of the OA1 gene, as well as the 5′ and 3′ untranslated regions, were scanned for point mutations in PCR-amplified DNA from 60 OA1 patients. The mutations identified include: two frameshifts and a splice site mutation leading to truncated OA1 proteins; a deletion of a threonine codon at position 290; and four missense mutations, two of which involve amino acids located within putative transmembrane domains. Two of the mutations each occur in three apparently unrelated families, consistent with previous observations of a founder effect in OA1. Surprisingly, mutations were detected in only one-third of the patients (21 of 60) ascertained. We postulate that mutations not yet identified in either regulatory elements of the OA1 gene, or in other gene(s) located within the same chromosomal region, may be a common cause of X-linked ocular albinism.

UR - http://www.scopus.com/inward/record.url?scp=0028852091&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=0028852091&partnerID=8YFLogxK

U2 - 10.1093/hmg/4.12.2319

DO - 10.1093/hmg/4.12.2319

M3 - Article

C2 - 8634705

AN - SCOPUS:0028852091

VL - 4

SP - 2319

EP - 2325

JO - Human Molecular Genetics

JF - Human Molecular Genetics

SN - 0964-6906

IS - 12

ER -