Mutation of the start codon in the FRDA1 gene: Linkage analysis of three pedigrees with the ATG to ATT transversion points to a unique common ancestor

Christine Zühlke; Franco Laccone; Mireille Cossée; Alfried Kohlschütter; Michel Koenig; Eberhard Schwinger

doi:10.1007/s004390050791

Mutation of the start codon in the FRDA1 gene: Linkage analysis of three pedigrees with the ATG to ATT transversion points to a unique common ancestor

Christine Zühlke^*, Franco Laccone, Mireille Cossée, Alfried Kohlschütter, Michel Koenig, Eberhard Schwinger

^*Corresponding author for this work

Institute of Human Genetics

23 Citations (Scopus)

Abstract

Friedreich ataxia (FRDA) is a progressive neurodegenerative disorder caused by loss-of-function mutations in the gene encoding frataxin. Most patients with FRDA have trinucleotide repeat expansions in both alleles of the FRDA1 gene. In patients heterozygous for the expansion the second allele may be inactivated by a point mutation. We identified the ATG→ATT (M1I) mutation of the start codon in three independent families. Individuals with symptoms of FRDA in these families are compound heterozygous for the repeat expansion and the ATG mutation. To look for a common founder of the M1I mutation, a detailed linkage analysis employing six polymorphic chromosome 9 markers was performed. We found complete haplotype identity for two of the three chromosomes with the point mutation. The third case shows partial conformity and may be the result of a single recombination event.

Original language	English
Journal	Human Genetics
Volume	103
Issue number	1
Pages (from-to)	102-105
Number of pages	4
ISSN	0340-6717
DOIs	https://doi.org/10.1007/s004390050791
Publication status	Published - 1998

Funding

families for providing blood samples for scientific research. C.Z. thanks H. Böttger and U. Gehlken for excellent technical assistance. This work was supported by the Forschungsförderungsprogramm der Medizinischen Universität Lübeck (89/96) and the Association Franc-aise contre les Myopathies, CNRS, INSERM, CHRU de Strasbourg, and the Ministere de l’Enseignement Superieur et de la Recherche.

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Research Area: Medical Genetics

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10.1007/s004390050791

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title = "Mutation of the start codon in the FRDA1 gene: Linkage analysis of three pedigrees with the ATG to ATT transversion points to a unique common ancestor",

abstract = "Friedreich ataxia (FRDA) is a progressive neurodegenerative disorder caused by loss-of-function mutations in the gene encoding frataxin. Most patients with FRDA have trinucleotide repeat expansions in both alleles of the FRDA1 gene. In patients heterozygous for the expansion the second allele may be inactivated by a point mutation. We identified the ATG→ATT (M1I) mutation of the start codon in three independent families. Individuals with symptoms of FRDA in these families are compound heterozygous for the repeat expansion and the ATG mutation. To look for a common founder of the M1I mutation, a detailed linkage analysis employing six polymorphic chromosome 9 markers was performed. We found complete haplotype identity for two of the three chromosomes with the point mutation. The third case shows partial conformity and may be the result of a single recombination event.",

author = "Christine Z{\"u}hlke and Franco Laccone and Mireille Coss{\'e}e and Alfried Kohlsch{\"u}tter and Michel Koenig and Eberhard Schwinger",

note = "Funding Information: families for providing blood samples for scientific research. C.Z. thanks H. B{\"o}ttger and U. Gehlken for excellent technical assistance. This work was supported by the Forschungsf{\"o}rderungsprogramm der Medizinischen Universit{\"a}t L{\"u}beck (89/96) and the Association Franc-aise contre les Myopathies, CNRS, INSERM, CHRU de Strasbourg, and the Ministere de l{\textquoteright}Enseignement Superieur et de la Recherche.",

year = "1998",

doi = "10.1007/s004390050791",

language = "English",

volume = "103",

pages = "102--105",

journal = "Human Genetics",

issn = "0340-6717",

publisher = "Oxford University Press",

number = "1",

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T1 - Mutation of the start codon in the FRDA1 gene: Linkage analysis of three pedigrees with the ATG to ATT transversion points to a unique common ancestor

AU - Zühlke, Christine

AU - Laccone, Franco

AU - Cossée, Mireille

AU - Kohlschütter, Alfried

AU - Koenig, Michel

AU - Schwinger, Eberhard

N1 - Funding Information: families for providing blood samples for scientific research. C.Z. thanks H. Böttger and U. Gehlken for excellent technical assistance. This work was supported by the Forschungsförderungsprogramm der Medizinischen Universität Lübeck (89/96) and the Association Franc-aise contre les Myopathies, CNRS, INSERM, CHRU de Strasbourg, and the Ministere de l’Enseignement Superieur et de la Recherche.

PY - 1998

Y1 - 1998

N2 - Friedreich ataxia (FRDA) is a progressive neurodegenerative disorder caused by loss-of-function mutations in the gene encoding frataxin. Most patients with FRDA have trinucleotide repeat expansions in both alleles of the FRDA1 gene. In patients heterozygous for the expansion the second allele may be inactivated by a point mutation. We identified the ATG→ATT (M1I) mutation of the start codon in three independent families. Individuals with symptoms of FRDA in these families are compound heterozygous for the repeat expansion and the ATG mutation. To look for a common founder of the M1I mutation, a detailed linkage analysis employing six polymorphic chromosome 9 markers was performed. We found complete haplotype identity for two of the three chromosomes with the point mutation. The third case shows partial conformity and may be the result of a single recombination event.

AB - Friedreich ataxia (FRDA) is a progressive neurodegenerative disorder caused by loss-of-function mutations in the gene encoding frataxin. Most patients with FRDA have trinucleotide repeat expansions in both alleles of the FRDA1 gene. In patients heterozygous for the expansion the second allele may be inactivated by a point mutation. We identified the ATG→ATT (M1I) mutation of the start codon in three independent families. Individuals with symptoms of FRDA in these families are compound heterozygous for the repeat expansion and the ATG mutation. To look for a common founder of the M1I mutation, a detailed linkage analysis employing six polymorphic chromosome 9 markers was performed. We found complete haplotype identity for two of the three chromosomes with the point mutation. The third case shows partial conformity and may be the result of a single recombination event.

UR - https://www.scopus.com/pages/publications/0031683863

U2 - 10.1007/s004390050791

DO - 10.1007/s004390050791

M3 - Journal articles

C2 - 9737785

AN - SCOPUS:0031683863

SN - 0340-6717

VL - 103

SP - 102

EP - 105

JO - Human Genetics

JF - Human Genetics

IS - 1

ER -

Mutation of the start codon in the FRDA1 gene: Linkage analysis of three pedigrees with the ATG to ATT transversion points to a unique common ancestor

Abstract

Funding

Research Areas and Centers

UN SDGs

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