Advertisement

Prenatal diagnosis of Menkes disease by genetic analysis and copper measurement

      Abstract

      Carrier detection for 12 women and prenatal diagnosis for six fetuses in Japanese families with a patient with Menkes disease (MNK) were performed by gene analysis and/or measurement of the copper concentration in cultured cells. Six out of eight mothers of MNK patients were carriers while two (25%) were not carriers. Two unrelated patients showed the same mutation (R986X): one patient's mother was a carrier while the other was not. One male and three female fetuses did not have the same mutant allele as the respective MNK proband and have been healthy since birth. One female fetus had the same mutant allele as her affected brother. Gene analysis is very useful and reliable, although such examination is only indicated in families in which a mutation has been identified. In one family in which a mutation in ATP7A was not found, cultured amniocytes from a male fetus had a high copper concentration. Thus after his birth, the biochemical findings confirmed the presence of MNK and early treatment was started. As his early treatment with parenteral copper-histidine prevented the neurological disorders effectively, prenatal diagnosis is very important.

      Keywords

      To read this article in full you will need to make a payment

      Purchase one-time access:

      Academic & Personal: 24 hour online accessCorporate R&D Professionals: 24 hour online access
      One-time access price info
      • For academic or personal research use, select 'Academic and Personal'
      • For corporate R&D use, select 'Corporate R&D Professionals'

      Subscribe:

      Subscribe to Brain and Development
      Already a print subscriber? Claim online access
      Already an online subscriber? Sign in
      Institutional Access: Sign in to ScienceDirect

      References

        • Kodama H.
        • Murata Y.
        • Kobayashi M.
        Clinical manifestations and treatment of Menkes disease and its variants.
        Pediatr Int. 1999; 41: 423-429
        • Horn N.
        Menkes' X-linked disease: prenatal diagnosis and carrier detection.
        J Inherit Metab Dis. 1983; 6: 59-62
        • Heydorn K.
        • Damsgaard E.
        • Horn N.
        Accumulated experience with prenatal diagnosis of Menkes disease by neutron activation analysis of chorionic villi specimens.
        Biol Trace Elem Res. 1999; 71–72: 551-561
        • Gu Y.H.
        • Kodama H.
        • Murata Y.
        • Mochizuki D.
        • Yanagawa Y.
        • Ushijima H.
        • et al.
        ATP7A gene mutations in 16 patients with Menkes disease and a patient with occipital horn syndrome.
        Am J Med Genet. 2001; 99: 217-222
        • Ogawa A.
        • Yamamoto S.
        • Takayanagi M.
        • Kogo T.
        • Kanazawa M.
        • Kohno Y.
        Identification of three novel mutations in the MNK gene in three unrelated Japanese patients with classical Menkes disease.
        J Hum Genet. 1999; 44: 206-209
        • Tümer Z.
        • Møller L.B.
        • Horn N.
        Mutation spectrum of ATP7A, the gene defective in Menkes disease.
        Adv Exp Med Biol. 1999; 448: 83-95
        • Nussbaum R.L.
        • McInnes R.R.
        • Willard H.F.
        Genetic variation in populations.
        in: Nussbaum R.L. McInnes R.R. Willard H.F. Thompson and Thompson genetics in medicine. 6th ed. W.B. Saunders, Philadelphia, PA2001: 95-105
        • Das S.
        • Whitney S.
        • Taylor J.
        • Chen E.
        • Levinson B.
        • Vulpe C.
        • et al.
        Prenatal diagnosis of Menkes disease by mutation analysis.
        J Inher Metab Dis. 1995; 18: 364-365
        • Tümer Z.
        • Tønnesen T.
        • Böhmann J.
        • Marg W.
        • Horn N.
        First trimester prenatal diagnosis of Menkes disease by DNA analysis.
        J Med Genet. 1994; 31: 615-617
        • Tümer Z.
        • Horn N.
        Menkes disease: recent advances and new aspects.
        J Med Genet. 1997; 34: 265-274