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1.
The infantile form of glycerol kinase (GK) deficiency (McKusick No. 30703) (1) is characterized by adrenal cortical insufficiency, adrenal hypoplasia and developmental delay. The underlying biochemical mechanism(s) responsible for the observed clinical presentations are undetermined. Pursuant to our examination of the molecular pathogenesis of this enzyme deficiency, we have endeavored to develop a model for this disorder. 1-thioglycerol (1-TG) was investigated as a potential GK inhibitor in adrenal gland, an organ consistently affected, and in cultured fibroblasts, available from affected individuals. In 105,000 g bovine adrenal supernatant the Ki for 1-TG was 1.9 mM. In human fibroblast 105,000 g supernatant, the Ki for 1-TG was 3.4 mM. In both tissues the inhibition was purely competitive with respect to glycerol. Using incorporation of [14C(U)]-glycerol into protein as an index of GK activity in situ in human skin fibroblasts, GK deficient fibroblasts incorporate less than 10% of that observed in normal fibroblasts. Addition of 1-TG to normal fibroblasts resulted in inhibited incorporation rates. The specificity of these effects in situ was examined. Our findings indicate that 1-TG may be a suitable inhibitor of GK activity for the development of a model for glycerol kinase deficiency. 相似文献
2.
We present here a 13-year-old male with hypopituitarism which accompanied an insidious and gradual progress of ACTH deficiency. ACTH deficiency finally led to an overt crisis of adrenal insufficiency at the age of 12 years and 7 months. This patient is unique because the insidious and gradual progress has been proved by not only the laboratory results but also the clinical course for over 13 years. The cause of panhypopituitarism including ACTH deficiency is thought to have existed before or at the delivery because of the stalk transection seen on the magnetic resonance image (MRI). At the crisis, his laboratory results suggested that he had secondary adrenal insufficiency, whereas he showed normal adrenal function proved by the insulin tolerance test (ITT) at the age of 4 years. Abrupt crisis of secondary adrenal insufficiency developed at the age of 12 years, although he had been well until the crisis. 相似文献
3.
Adrenal and testicular function in 14 patients with adrenoleukodystrophy or adrenomyeloneuropathy 总被引:1,自引:0,他引:1
Testicular and adrenal function were evaluated in 12 patients with adrenoleukodystrophy and 2 patients with adrenomyeloneuropathy. Although only 5 subjects had clinical symptoms suggesting adrenal insufficiency, an additional 5 showed laboratory evidence of reduced adrenal reserve. 9 of the 14 patients developed neurological deficits prior to the onset of clinical or biological adrenal insufficiency. In the remaining 5 patients, adrenal insufficiency antedated the appearance of neurological symptoms; 2 of these 5 patients had only laboratory evidence of hypoadrenocorticism, and 3 had both clinical and laboratory abnormalities. None of the prepubertal patients had detectable signs of testicular insufficiency, while 3 of the 7 pubertal/adult patients had elevated serum LH or FSH levels. This mild testicular deficiency was seen only in association with clinical adrenal insufficiency and significant neurological impairment. 相似文献
4.
OBJECTIVE: X-linked adrenal hypoplasia congenita (AHC) is a condition clinically featuring adrenal insufficiency and hypogonadotropic hypogonadism caused by mutations of DAX-1. This study was undertaken to characterize the molecular defects of DAX-1 in 3 unrelated Korean patients with AHC. PATIENTS AND METHODS: Patient 1 is a 6-year-old boy who presented with a salt-losing adrenal crisis in the neonatal period. Patient 2 is a 3-year-old boy who manifested aspiration pneumonia and adrenal insufficiency at the age of 1 month. Patient 3 is a 7-year-old boy who developed an adrenal crisis at the age of 3 days. In each of these patients, DAX-1 was analyzed by direct DNA sequencing after polymerase chain reaction amplification of the entire coding region. RESULTS: Direct sequencing of DAX-1 revealed two novel mutations, 1156_1157delCT in patient 1 and another novel nonsense mutation W105X in patient 2. Patient 3 had complete deletion of DAX-1. In patient 3, serum transaminases and creatine kinase levels were elevated while the glycerol kinase activity of leukocytes was decreased. Markedly elevated glycerol excretion was detected by urine organic acid analysis. Patient 3 was diagnosed as Xp21 contiguous gene syndrome associated with deletions of the entire IL1RAPL, GK genes and the C-terminal region of DMD gene. CONCLUSIONS: Two novel mutations of DAX-1 were detected in 2 unrelated patients with AHC, and complete deletion of DAX-1 in a patient with Xp21 contiguous gene syndrome who also presented with glycerol kinase deficiency, Duchenne muscular dystrophy, and AHC. 相似文献
5.
Adrenal dysfunction in glycerol kinase deficiency 总被引:2,自引:0,他引:2
W K Seltzer H Firminger J Klein A Pike P Fennessey E R McCabe 《Biochemical medicine》1985,33(2):189-199
The infantile form of glycerol kinase deficiency appears to be an X-linked disorder which is consistently characterized by developmental delay and adrenal cortical insufficiency and hypoplasia. We propose that the inherited deficiency of outer mitochondrial membrane-bound glycerol kinase restricts glycerophospholipid synthesis, and, hence, the activation of steroidogenesis. This would limit the conversion of cholesterol to pregnenolone, the precursor for glucocorticoids in the adrenal cortex. The deficiency in cortisol production, with a lack of feedback to the pituitary, would result in increased ACTH production and hypertrophy of the fascicular zone at the same time that replication of the cells within this zone would be inhibited. Similarly, the decreased mineralocorticoid production by the sparse glomerulosal zone would limit the ability of the individual to respond to stress, and would result in development of potentially fatal hyponatremia and hyperkalemia. Organization of the pathway for glycerophospholipid synthesis at the outer mitochondrial membrane would make this pathway particularly vulnerable to mutations disrupting the compartmented production of the parent compound, glycerol 3-phosphate, by mitochondrial-bound glycerol kinase. 相似文献
6.
Human and rat adrenal glycerol kinase: subcellular distribution and bisubstrate kinetics 总被引:1,自引:0,他引:1
Summary The subcellular distribution of adrenal glycerol kinase in man and rat are reported and the bisubstrate kinetics of the soluble enzyme are compared in these two species. The specific activity of glycerol kinase in human whole adrenal homogenate (145 µU/mg protein) was 3 times that found in rat whole adrenal homogenate (48 µU/mg protein). In both species 8% of the total glycerol kinase activity was associated with the nuclear pellet fraction. In human, 62% of the total activity was soluble, while 24% was associated with the postnuclear particulate fraction. Rat glycerol kinase activity was also predominantly soluble: 69% of the total activity was soluble and 13% was in the postnuclear particulate fraction. The apparent Km for glycerol in soluble adrenal glycerol kinase was similar in both species, 2.8 µM in human and 3.1 µM in rat. The apparent Km for ATP in soluble human adrenal glycerol kinase was 22.0 µM. In rat the enzyme did not appear to follow Michaelis-Menten kinetics with ATP as substrate. The Vmax for the soluble enzyme was similar in both human and rat.This report provides a background to biochemical investigations on human glycerol kinase deficiency, an inborn error of metabolism which may be characterized by adrenal hypoplasia and insufficiency. 相似文献
7.
Characterization of patients with glycerol kinase deficiency utilizing cDNA probes for the Duchenne muscular dystrophy locus 总被引:3,自引:0,他引:3
Jeffrey A. Towbin Darong Wu Jeffrey Chamberlain Paul D. Larsen William K. Seltzer Edward R. B. McCabe 《Human genetics》1989,83(2):122-126
Summary Genomic DNA from five previously unreported patients with glycerol kinase deficiency (GKD), dystrophic myopathy, and adrenal insufficiency were studied with genomic probes and cDNA probes for the Duchenne muscular dystrophy (DMD) locus. These individuals, together with those reported by ourselves and others, show that patients with a contigous gene syndrome involving the DMD, GK, and adrenal hypoplasia congenita (AHC) loci have a broader distribution of microdeletion breakpoints than those observed among patients with classical DMD. This study demonstrates the use of the DMD cDNA probes to delineate the centromeric deletion breakpoints for patients with Xp21 microdeletions extending beyond the DMD locus. It also shows the practical diagnostic application of the DMD cDNA probes when the diagnosis of GKD is entertained in a patient with known DMD and only DNA is available for study. 相似文献
8.
Dipple KM Zhang YH Huang BL McCabe LL Dallongeville J Inokuchi T Kimura M Marx HJ Roederer GO Shih V Yamaguchi S Yoshida I McCabe ER 《Human genetics》2001,109(1):55-62
Glycerol kinase deficiency (GKD) occurs as part of an Xp21 contiguous gene syndrome or as isolated GKD. The isolated form can be either symptomatic with episodic metabolic and central nervous system (CNS) decompensation or asymptomatic with hyperglycerolemia and glyceroluria only. To better understand the pathogenesis of isolated GKD, we sought individuals with point mutations in the GK coding region and measured their GK enzyme activities. We identified six individuals with missense mutations: four (N288D, A305V, M428T, and Q438R) among males who were asymptomatic and two (D198G, R405Q) in individuals who were symptomatic. GK activity measured in lymphoblastoid cell lines or fibroblasts was similar for the symptomatic and the asymptomatic individuals. Mapping of the individuals' missense mutations to the three-dimensional structure of Escherichia coli GK revealed that the symptomatic individuals' mutations are in the same region as a subset of the mutations among the asymptomatic individuals, adjacent to the active-site cleft. We conclude that, like many other disorders, GK genotype does not predict GKD phenotype. We hypothesize that the phenotype of an individual with GKD is a complex trait influenced by additional, independently inherited genes. 相似文献
9.
《Endocrine practice》2016,22(1):30-35
Objective: Primary adrenal insufficiency is a life-threatening endocrine disease unless properly treated. However, few studies on the prevalence, concomitances of the disease, and prescribing of drugs have been published. The goal of the study was to establish the prevalence of primary adrenal insufficiency in Iceland and additionally, to study the most common concomitant diseases in patients with primary adrenal insufficiency, as well as the mode of glucocorticoid replacement therapies.Methods: To achieve this, the medical records of all patients in Iceland who had received the International Classification of Diseases and Related Health Problems, 10th Revision, diagnosis code E27, were evaluated for true primary adrenal insufficiency. Additionally, these records were evaluated for concomitant diseases, as well as the mode of glucocorticoid replacement therapy. The study covered the whole population of Iceland over 18 years of age. It was thus a nationwide study. The records were retrieved from large hospitals and clinics and every practicing specialist in endocrinology.Results: Primary adrenal insufficiency was found in 53 individuals, 26 women and 27 men, yielding a prevalence of 22.1 per 100,000 population. Hypothyroidism was by far the most common concomitant disease. Most patients had their glucocorticoid deficiency replaced with shortacting glucocorticoids.Conclusion: The prevalence of primary adrenal insufficiency in Iceland is higher than in earlier reports, with comorbidities being in line with recent studies. Treatment is according to the latest protocols.Abbreviations:CAH = congenital adrenal hyperplasiaCVD = cardiovascular diseaseDM = diabetes mellitusGC = glucocorticoidLSH = Landspitali National University HospitalPAI = primary adrenal insufficiencyPAS = polyendocrine autoimmune syndrome 相似文献
10.
Six patients with Cushing's disease and three with Cushing's syndrome due to an adrenal adenoma were monitored after their adenomectomy with the corticotropin-releasing hormone test to evaluate the progress of recovery of their pituitary adrenal function. Before surgery the patients with Cushing's disease showed either high, normal or low responses of plasma ACTH and cortisol to 100 micrograms synthetic ovine corticotropin-releasing hormone (CRH) administered intravenously, whereas all three patients with Cushing's syndrome due to an adrenal adenoma showed no response of plasma ACTH or cortisol to CRH. One or two months after surgery, the patients who had Cushing's disease had low levels of basal plasma ACTH and cortisol and their responses to CRH were extremely low. However, the same patients were tested later, it was found that their responses to CRH gradually increased and reached normal ranges approximately within one year after tumor removal, which coincided with the overall improvement in their clinical signs and symptoms due to adrenal insufficiency. In contrast, the recovery of the pituitary adrenal function in patients who had Cushing's syndrome due to an adrenal adenoma was not complete even one year after surgery. Thus the corticotropin-releasing factor test is a useful criteria to evaluate the recovery of the pituitary adrenal function in these patients after surgery, since the responses of plasma ACTH and cortisol to the administered CRH are parallel with the improvements in clinical signs and symptoms due to adrenal insufficiency in patients with Cushing's disease. 相似文献
11.
Androgens are defined as the steroids having a binding affinity of the androgen receptor. In the reproduction age a daily production of testosterone is equally divided between the ovaries and adrenal and local tissue conversion of androstenedione and DHEA. After menopause the 80% of testosterone is produced in ovaries, but majority of precursors for peripheral conversion is adrenal origin. Androgen receptors are present throughout in the body; over 200 cellular actions of androgens have been described. Androgenic action is determined by quantitative level of the androgen present in the circulation, its degree of binding to proteins, the degree of interconversion to other androgens and estrogens, and the biological potency and androgen receptor binding affinity of the androgen. The most common clinical symptoms of androgen deficiency are the reduction of sex motivation, sex fantasy, sex enjoyment, sex arousal, vaginal vasocongestion, but also reduction of pubic hair, bone mass, muscle mass, worsening of quality of life (mood, affect, energy), more frequent vasomotors symptoms, insomnia, depression, headache. All these signs and symptoms can be multifactorial. Most common conditions associated with hypoandrogenism in women are hypothalamic-pituitary abnormalities, lack or insufficiency of ovaries, adrenal insufficiency, glucocorticoid therapy, exogenous estrogen administration. Besides the clinical picture the free testosterone measuring is important for diagnosis. The method of choice of this measure is equilibrium dialysis assay. Despite of clinical importance of androgen insufficiency in women, none of methods of androgen substitution is approved by FDA. 相似文献
12.
《Endocrine practice》2015,21(4):395-399
Objective: The American Association of Clinical Endocrinologists Adrenal Scientific Committee has developed a series of articles to update members on the genetics of adrenal diseases.Methods: Case presentation, discussion of literature, table, and bullet point conclusions.Results: The genetic mutations associated with several familial causes of adrenal insufficiency have now been identified. The most common ones that will be discussed here include Allgrove syndrome, adrenoleukodystrophy, adrenal hypoplasia congenita, autoimmune polyglandular syndrome type 1, congenital adrenal hyperplasia (CAH), lipoid CAH, and familial glucocorticoid deficiency. Although these diseases most commonly present in childhood, some rarely present in adulthood, and thus all endocrinologists must be familiar with these syndromes. Some patients only develop glucocorticoid deficiency, and others have both glucocorticoid and mineralocorticoid deficiency. These diseases may be associated with other conditions, especially neurologic disease, hypogonadism, or dermatologic problems. Diagnosis is suspected based on clinical presentation and laboratory findings. Gene testing may be necessary for confirmation of a diagnosis and/or screening of family members.Conclusion: This article briefly reviews the various familial adrenal insufficiency syndromes and the specific associated gene defects.Abbreviations: AAA = Allgrove syndrome (alachrima-achalasiaadrenal insufficiency) ACTH = adrenocorticotropic hormone AHC = adrenal hypoplasia congenita ALD = adrenoleukodystrophy CAH = congenital adrenal hyperplasia DAX1 = dosage-sensitive sex reversal, adrenal hypoplasia congenita, X-chromosome FGD = familial glucocorticoid deficiency LCAH = lipoid CAH MCM4 = mini-chromosome maintenancedeficient 4 SF1 = steroidogenic factor 1 VLCFA = very-long-chain fatty acid 相似文献
13.
Two amenorrheic women presenting clinical signs of adrenal insufficiency were shown to have isolated corticotropin deficiency (ICD). LH and FSH were normally responsive to GnRH. The occurrence of this disease during the postpartum and the presence of autoantibodies against corticotropic cells in one case may indicate that ICD was a sequela of an autoimmune hypophysitis. The presence of amenorrhea, while the gonadotroph was not damaged, and the reappearance of ovulatory menstrual cycles under the sole effect of hydrocortisone replacement therapy suggest that cortisol deficiency may by itself alter the gonadal function. 相似文献
14.
Lesions in the gene encoding the adrenal enzyme steroid 21-hydroxylase (P450c21) result in defective adrenal cortisol synthesis, often accompanied by aldosterone deficiency. The symptoms range from severe neonatal disease to inconspicuous symptoms in adulthood depending on the nature of the mutations. The 21-hydroxylase gene is present in close proximity to a highly homologous pseudogene, and both genes show variation in copy number between individuals. For complete DNA sequence characterization, we have applied selective polymerase chain reaction amplification and direct sequencing of all full-length steroid 21-hydroxylase genes present in individuals. Using healthy individuals with only one remaining steroid 21-hydroxylase allele as normal references, a new allele was found in two siblings, in whom clinical and laboratory findings demonstrated moderate enzyme deficiency. Full-length sequencing of this allele displayed an Arg 484 to Pro codon change in exon 10, in the same position as a previously identified GG to C mutation found in a patient with severe 21 -hydroxylase deficiency. Arg 484 is located within a stretch of amino acids that are highly conserved between mammalian 21-hydroxylases. The finding of the presently reported 21-hydroxylase allele indicates that the GG to C mutation from the severely affected patient has arisen by a two-step mechanism, consisting of a G to C transversion accompanied by an adjacent G deletion. When sequencing 26 pseudogenes, both these mutations, which are not present in the pseudogenes hitherto reported, were found at low frequency together with a number of other polymorphisms. Thus, also rare mutations can spread via the pseudogene and can therefore be expected to arise independently in unrelated individuals. 相似文献
15.
HLA linkage and B14, DR1, BfS haplotype association with the genes for late onset and cryptic 21-hydroxylase deficiency.
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M S Pollack L S Levine G J O'Neill S Pang F Lorenzen B Kohn G F Rondanini G Chiumello M I New B Dupont 《American journal of human genetics》1981,33(4):540-550
Classical congenital adrenal hyperplasia due to 21-hydroxylase deficiency (21-OH-def) has been established to be an HLA-linked, recessive monogenetic disease. However, two nonclassical forms of 21-OH-def have also been described: "cryptic" 21-OH-def, which has been shown to be HLA-linked, and "late onset" 21-OH-def, for which the status of linkage to HLA has been less certain. We now describe studies of eight additional unrelated probands with symptomatic, "late onset" 21-OH-def, and conclude that this form is also HLA-linked. Both "late onset" and "cryptic" 21-OH-def are highly associated with the same HLA antigens and markers (HLA-B14, HLA-DR1, and Bf type S) in individuals from different ethnic and geographical backgrounds. Since both "late onset" and "cryptic" 21-OH-def appear to occur in individuals with one classical 21-OH-def (21-OHCAH) allele who in addition have another 21-OH-def allele, as well as in individuals who appear to be homozygous for variant 21-PH-def alleles, and since both late onset and cryptic 21-OH-def appear to occur in the same families, our data suggest that these syndromes may represent different clinical expressions of similar or identical nonclassical 21-OH-def alleles. 相似文献
16.
John L. Graner 《CMAJ》1985,133(9):855-857,880
In 1849 Thomas Addison described the clinical entity now known as pernicious anemia. In 1855 he reported several cases of adrenal insufficiency, or Addison''s disease. Considering the importance of these works, there remains a great deal of confusion about them. Contrary to what many historians have written, a review of Addison''s original publications demonstrates a firm appreciation of the distinction between pernicious anemia and adrenal insufficiency, based particularly on the discoloration of the skin in these conditions. Three major sources of possible confusion for historians who are attempting to understand Addison''s views include Addison''s early attempts to link pernicious anemia with disease of the supra-renal capsules, Addison''s redefinition of pernicious anemia in his monograph on adrenal disease, and several confusing statements made by Wilks and Daldy in the first reprint of Addison''s monograph. 相似文献
17.
Glycerol kinase plays a critical role in metabolism by converting glycerol to glycerol 3-phosphate in an ATP dependent reaction. In humans, glycerol kinase deficiency results in a wide range of phenotypic variability; patients can have severe metabolic and CNS abnormalities, while others possess hyperglycerolemia and glyceroluria with no other apparent phenotype. In an effort to help understand the pathogenic mechanisms underlying the phenotypic variation, we have created a Drosophila model for glycerol kinase deficiency by RNAi targeting of dGyk (CG18374) and dGK (CG7995). As expected, RNAi flies have reduced glycerol kinase RNA expression, reduced phosphorylation activity and elevated glycerol levels. Further investigation revealed these flies to be hypersensitive to fly food supplemented with glycerol. Due to the hygroscopic nature of glycerol, we predict glycerol hypersensitivity is a result of greater susceptibility to desiccation, suggesting glycerol kinase to play an important role in desiccation resistance in insects. To evaluate a role for genetic modifier loci in determining severity of the glycerol hypersensitivity observed in knockdown flies, we performed a preliminary screen of lethal transposon insertion mutant flies using a glycerol hypersensitive survivorship assay. We demonstrate that this type of screen can identify both enhancer and suppressor genetic loci of glycerol hypersensitivity. Furthermore, we found that the glycerol hypersensitivity phenotype can be enhanced or suppressed by null mutations in eye pigmentation genes. Taken together, our data suggest proteins encoded by eye pigmentation genes play an important role in desiccation resistance and that eye pigmentation genes are strong modifiers of the glycerol hypersensitive phenotype identified in our Drosophila model for glycerol kinase deficiency. 相似文献
18.
We have identified eight individuals in an Amish population in Geauga County, Ohio, who have a congenital hemolytic anemia and red cell pyruvate kinase (PK) deficiency. The mutant enzyme is a low Km phosphoenolpyruvate (PEP) variant associated with a slower (77.5% of normal) electrophoretic mobility in starch gel. Because of the high consanguinity in this population, we assume the affected individuals are homozygous for the mutant gene. Genealogical records allow us to trace all eight cases back to a common ancestor who lived in Mifflin County, Pennsylvania. His sister was a common ancestor to all cases of PK deficiency originally described in the Pennsylvania Amish isolate. Therefore, all cases of PK deficiency in the Amish arose from a common ancestral pair. 相似文献
19.
Belsy Guerrero Hector J. Finol Matias Reyes-Lugo Ana M. Salazar Elda E. Sánchez Amalid Estrella Antonio Roschman-González Carlos Ibarra Ivan Salvi Alexis Rodríguez-Acosta 《Comparative biochemistry and physiology. Toxicology & pharmacology : CBP》2010,151(1):113-121
Brown widow spider (BrWS) (Latrodectus geometricus) venom produces intense systemic reactions such as cramps, harsh muscle nociceptive, nauseas, vomiting and hypertension. The proposed pathogenic mechanisms resulting in these accidents have principally been damages occurring at the nervous system. However, it is suspected that there is also damage of the adrenal glands, as a result of the experimental animal's clinical manifestations, which developed symptoms compatible with acute adrenal insufficiency. We have currently found that the adrenal gland is damaged by this venom gland homogenates (VGH) producing severe alterations on cortex cells resulting in death by acute adrenal insufficiency. In general, the ultrastructural study on the glands of mice under transmission electronic microscopy observations showed alterations in the majority of the intracellular membranes within 3 to 24 h. BrWSVGH also showed specific actions on extracellular matrix proteins such as fibronectin, laminin and fibrinogen. In addition, zymogram experiments using gelatin as substrates detected gelatinolytic activity. The molecular exclusion fractionation of crude BrWSVGH resulted in 15 fractions, of which F1 and F2 presented α/β-fibrinogenase and fibronectinolytic activities. Fractions F6, F14 and F15 showed only α-fibrinogenase activity; in contrast, the gelatinolytic action was only observed in fraction F11. Only metalloproteinase inhibitors abolished all these proteolytic activities. Our results suggest that adrenal cortex lesions may be relevant in the etiopathogenesis of severe brown widow spider envenoming. To our knowledge, this is the first report on adrenal gland damages, fibrinogenolytic activity and interrelations with cell-matrix adhesion proteins caused by L.geometricus VGH. The venom of this spider could be inducing hemostatic system damages on envenomed patients. 相似文献
20.
Myopathy in complex glycerol kinase deficiency patients is due to 3'' deletions of the dystrophin gene. 总被引:6,自引:4,他引:2
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DNA samples from nine previously reported patients with X-linked recessive glycerol kinase deficiency, associated in seven of them with adrenal hypoplasia and in five with developmental delay and myopathy, have been studied for deletions of the Duchenne/Becker muscular dystrophy gene by probing with the entire cDNA for the dystrophin protein. All five patients with myopathy, including two in whom no deletions had been detected before, were found to have variable-sized deletions extending through the 3' end of this gene. The 5' deletion breakpoints are intragenic in four cases and have been mapped precisely on the exon-containing HindIII fragment map. A correlation was found between severity and progression of the muscular dystrophy phenotype and the sizes of the gene deletions. In cases in which there was glycerol kinase deficiency/adrenal hypoplasia microdeletion syndrome without myopathy, no deletions were found with the dystrophin cDNA. 相似文献