Localization of a gene for molybdenum cofactor deficiency, on the short arm of chromosome 6, by homozygosity mapping

Adel Shalata, Hanna Mandel, Jochen Reiss, Raymonde Szargel, Annick Cohen-Akenine, Claude Dorche, Marie Therese Zabot, Albert Van Gennip, Nico Abeling, Moshe Berant, Nadine Cohen

Research output: Contribution to journalArticlepeer-review

14 Scopus citations

Abstract

Molybdenum cofactor deficiency (MoCoD) is a fatal disorder manifesting, shortly after birth, with profound neurological abnormalities, mental retardation, and severe seizures unresponsive to any therapy. The disease is a monogenic, autosomal recessive disorder, and the existence of at least two complementation groups suggests genetic heterogeneity. In humans, MoCoD leads to the combined deficient activities of sulfite oxidase, xanthine dehydrogenase, and aldehyde oxidase. By using homozygosity mapping and two consanguineous affected kindreds of Israeli-Arab origin, including five patients, we demonstrated linkage of a MoCoD gene to an 8-cM region on chromosome 6p21.3, between markers D6S1641 and D6S1672. Linkage analysis generated the highest combined LOD-score value, 3.6, at a recombination fraction of 0, with marker D6S1575. These results now can be used to perform prenatal diagnosis with microsatellite markers. They also provide the only tool for carrier detection of this fatal disorder.

Original languageEnglish
Pages (from-to)148-154
Number of pages7
JournalAmerican Journal of Human Genetics
Volume63
Issue number1
DOIs
StatePublished - Jul 1998
Externally publishedYes

Bibliographical note

Funding Information:
This work was supported by the Israel Ministry of Health (to N.C. and H.M.) and by the Joseph Alias Fund for Medical Research (to H.M.). A.S. was supported, in part, by a fellowship from the Galilee Society (the Arab National Society for Health Research and Services). We thank members of the Généthon laboratory, including Arnaud Lemainque, Sabine Fauré, Claire Rochette, and Maud Petit, for their assistance with initial genomic screening. The collaboration of the families is gratefully acknowledged.

Funding

This work was supported by the Israel Ministry of Health (to N.C. and H.M.) and by the Joseph Alias Fund for Medical Research (to H.M.). A.S. was supported, in part, by a fellowship from the Galilee Society (the Arab National Society for Health Research and Services). We thank members of the Généthon laboratory, including Arnaud Lemainque, Sabine Fauré, Claire Rochette, and Maud Petit, for their assistance with initial genomic screening. The collaboration of the families is gratefully acknowledged.

FundersFunder number
Arab National Society for Health Research and Services
Galilee Society
Israel Ministry of Health
Joseph Alias Fund for Medical Research

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