Summary
We report a case of a boy with Duchenne muscular dystrophy (DMD) associated with GK deficiency (GK), congenital adrenal hypoplasia (AHC), and mental retardation. Cytogenetic analysis of prometaphasic chromosomes revealed an interstitial chromosome deletion at Xp21.2 possibly extending to Xp21.1 or Xp21.3. His phenotypically normal mother was heterozygous for this deletion. DNA probe analysis on Southern blots showed that the deletion affected the following probe sites: 754, pERT 84, 21A, XJ2.3, pERT 87, JBir, and J66-H1, whereas L1, C7, and CX5.4 probes gave a normal signal. Pulse field gel electrophoresis after SfiI digestion did not show abnormal fragments with L1. These data are consistent with a deletion of about 4 megabases and indicate that the GK and AHC loci are proximal to L1 and distal to J66-H1.
Similar content being viewed by others
References
Aldridge, J, Kunkel LM, Bruns G, Tantravahi U, Lalande M, Brenster T, Moreau E, Wilson M, Bromley W, Rodrick T, Latt SA (1984) A strategy to reveal high frequence RFLPs along the human X chromosome. Am J Hum Genet 36:546–564
Bakker E, Hofker MH, Goor N, Mandel JL, Wrogemann K, Davies KE, Kunkel LM, Willard HF, Fenton WA, Sankuyl L, Majoor-Krakauer D, Essen AJ van, Jahoda JMG, Sachs ES, Van Ommen GJB, Pearson PL (1985) Prenatal diagnosis and carrier detection of Duchenne muscular dystrophy with closely linked RFLPs. Lancet II:655–658
Bartley JA, Miller DK, Hayford JT, McCabe ERB (1982) The concordance of X-linked glycerol kinase deficiency with X-linked adrenal hypoplasia in two families. Lancet II:733
Bartley JA, Patil S, Davenport S, Goldstein D, Piskens J (1986) Duchenne muscular dystrophy, glycerol kinase deficiency, and adrenal insufficiency associated with Xp21 interstitial deletion. J Pediatr 108:189–192
Bertelson CJ, Bartley JA, Monaco AM, Colletti-Feener C, Fischbeck K, Kunkel LM (1986) Localisation of Xp21 meiotic exchange points in Duchenne muscular dystrophy families. J Med Genet 23:531–537
Burmeister M, Lehrach H (1986) Long-range restriction map around the Duchenne muscular dystrophy gene. Nature 324:582–585
Clarke A, Roberts H, Thomas NST, Whitefield A, Williams J Harper PS (1986) Duchenne muscular dystrophy with adrenal insufficiency and glycerol kinase deficiency: high resolution cytogenetic analysis with molecular biochemical and clinical studies. J Med Genet 23:501–508
Dunger DB, Davies KE, Pembrey M, Lake B, Pearson P, Williams D, Whitfield A, Dillon MJD (1986) Deletion on the chromosome detected by direct DNA analysis in one of two unrelated boys with glycerol kinase deficiency, adrenal hypoplasia and Duchenne muscular dystrophy. Lancet I:585–587
Dutrillaux B, Lejeune J (1971) Sur les nouvelles techniques d'analyse du caryotype humain. CR Acad Sci [D] (Paris) 272:2638–2640
Francke U, Ochs HD, Martinville de B, Giacalone J, Lindgren V, Disteche C, Pagon RA, Hofker MH, Van Ommen GJB, Pearson PL, Wedgwood RJ (1985) Minor Xp21 chromosome deletion in a male associated with expression of Duchenne muscular dystrophy, chronic granulomatous disease, retinitis pigmentosa, and McLeod syndrome. Am J Hum Genet 37:250–267
Francke U, Harper JF, Darras BT, Cowan JM, McCase ERB, Hohlschaher A, Seltzer WK, Saito F, Goto J, Harpey JP, Wise JE (1987) Congenital adrenal hypoplasia, myopathy and glycerol kinase deficiency: molecular genetic evidence for deletions. Am J Hum Genet 40:212–227
Goussault Y, Turpin E, Neel D, Dreux C, Chanu B, Bakir R, Rouffy J (1982) Pseudo-hypertriglyceridemia caused by hyperglycerolemia due to congenital enzyme deficiency. Clin Chim Acta 123: 269–274
Hofker MH, Van Ommen GJB, Bakker E, Burmeister M, Pearson PL (1986a) Development of additional RFLP probes near the locus for Duchenne muscular dystrophy by cosmid cloning of the DXS84 (754) locus. Hum Genet 74:270–274
Hofker MH, Bergen AAB, Skraastad MI, Bakker E, Francke U, Wieringa B, Bartley J, Van Ommen GJB, Pearson PL (1986b) Isolation of a random cosmid clone, CX5, which defines a new polymorphic locus, DXS148, near the locus of Duchenne muscular dystrophy. Hum Genet 74:275–279
ISCN (1985) Cytogenet Cell Genet 21:50–57
Kunkel LM, Lalande M, Monaco A, Flint A, Middlesworth W, Latt SA (1985a) Construction of a human X-chromosome enriched phage library which facilitates analysis of specific loci. Gene 33:251–258
Kunkel LM, Monaco AP, Middlesworth W, Ochs HD, Latt SA, (1985b) Specific cloning of DNA fragments absent from the DNA of a male patient with X chromosomal deletion. Proc Natl Acad Sci USA 82:4778–4782
Marhens F, Chelly J, Kaplan JC, Lefrancois D, Harpey JP, Dutrillaux B (1987) Familial deletion of Xp21.2 with glycerol kinase deficiency and congenital adrenal hypoplasia. Hum Genet 77:379–383
Monaco AP, Bertelson CJ, Middlesworth W, Colleti CA, Aldridge J, Fischbeck KH, Barleh R, Pericak-Vance MA, Roses AD, Kunkel LM (1985) Detection of deletions spanning the Duchenne muscular dystrophy locus using a tightly linked DNA segment. Nature 316:842–845
Monaco A, Bertelson CJ, Colletti-Feener C, Kunkel LM (1987) Localization and cloning of Xp21 deletion breakpoints involved in muscular dystrophy. Hum Genet 75:221–227
Patil SF, Bartley JA, Murray JC, Ionasescu W, Pearson PL (1985) X-linked glycerol kinase, adrenal hypoplasia and myopathy maps at Xp21. Cytogenet Cell Genet 40:720–721
Ray PN, Bufall B, Duff C, Longan C, Kean V, Thompson MW, Sylvester JE, Gorski JL, Schmickel RD, Worton RG (1985) Cloning of breakpoint of an Xj21 translocation associated with Duchenne muscular dystrophy. Nature 318:672–675
Rose CI, Haines DSM (1978) Familial hyperglyceroluria. J Clin Invest 61:163–170
Saito F, Goto J, Kakinuma H, Nakamura F, Murayama S, Nakano I, Tonomura A (1986) Inherited Xp21 delection in a boy with complex glycerol kinase deficiency syndrome. Clin Genet 29:92–93
Southern EM (1975) Detection of specific sequences among DNA fragments separated by gel electrophoresis. J Mol Biol 98:503–517
Van Ommen GJB, Verkerk JMH, Hofner MH, Monaco AP, Kunkel LM, Ray P, Worton R, Wieringa B, Bakker E, Pearson PL (1986) A physical map of 4 million bp around the Duchenne muscular dystrophy gene on the human X chromosome. Cell 47:499–504
Van Ommen GBJ, Bertelson C, Ginjaar HB, Den Dunnen JT, Bakker E, Chelly J, Malton M, Van Essen AG, Bartley G, Kundel LM, Pearson PL (1988) Long-range genomic map of the Duchenne muscular dystrophy (DMD) gene; isolation and use of J66 (DXS 268), a distal introgenic marker. Genomics (in press)
Viegas-Péquignot E, Dutrillaux B (1978) Uhe methode simple pour obtenir des prophases et des prometaphases. Ann Génét (Paris) 21:122–125
Wieringa B, Hustinx T, Scheres J, Renier W (1986) Glycerol kinase deficiency syndrome explained as X-chromosomal deletion. Cytogenet Cell Genet 40:777A
Yates JRW, Gillard EF, Cooke A, Colgan JM, Evans TJ, Ferguson-Smith MA (1987) Localisation of the gene for congenital hypoplasia. J Med Genet 24:241 (abstr)
Author information
Authors and Affiliations
Rights and permissions
About this article
Cite this article
Chelly, J., Marlhens, F., Dutrillaux, B. et al. Deletion proximal to DXS68 locus (L1 probe site) in a boy with Duchenne muscular dystrophy, glycerol kinase deficiency, and adrenal hypoplasia. Hum Genet 78, 222–227 (1988). https://doi.org/10.1007/BF00291665
Received:
Issue Date:
DOI: https://doi.org/10.1007/BF00291665