Mutation frequencies for glycogen storage disease Ia in the Ashkenazi Jewish population.

Dor Yeshorim, The Committee for the Prevention of Jewish Genetic Diseases, Brooklyn, New York, USA.
American Journal of Medical Genetics Part A (Impact Factor: 2.05). 09/2004; 129A(2):162-4. DOI: 10.1002/ajmg.a.30232
Source: PubMed

ABSTRACT Glycogen storage disease type Ia (GSDIa) is a severe autosomal recessive disorder caused by deficiency of the enzyme D-glucose-6-phosphatase (G6Pase). While numerous mutations have been found in cosmopolitan European populations, Ashkenazi Jewish (AJ) patients appear to primarily carry the R83C mutation, but possibly also the Q347X mutation found generally in Caucasians. To determine the frequency for both these mutations in the AJ population, we tested 20,719 AJ subjects for the R83C mutation and 4,290 subjects for the Q347X mutation. We also evaluated the mutation status of 30 AJ GSDIa affected subjects. From the carrier screening, we found 290 subjects with R83C, for a carrier frequency for this mutation of 1.4%. This carrier frequency translates into a predicted disease prevalence of 1 in 20,000, five times higher than for the general Caucasian population, confirming a founder effect and elevated frequency of GSDIa in the AJ population. We observed no carriers of the Q347X mutation. Among the 30 GSDIa affected AJ subjects, all were homozygous for R83C. These results indicate that R83C is the only prevalent mutation for GSDIa in the Ashkenazi population.

1 Bookmark
  • [Show abstract] [Hide abstract]
    ABSTRACT: Smog chamber FTIR techniques were used to study the atmospheric oxidation of methyl propionate in 740 Torr of air in the presence of NOx at 296 ± 2K. Relative rate techniques were used to measure k(OH + CH3CH2C(O)OCH3) = (9.29 ± 1.13) × 10-13, k(Cl + CH3CH2C(O)OCH3) = (1.51 ± 0.22) × 10-11, k(Cl + CH3CH2C(O)OC(O)H) = (2.89 ± 0.35) × 10-12, k(Cl + CH3CH2C(O)OH) = (4.72 ± 0.62) × 10-12, and k(Cl + CH3C(O)C(O)OCH3) = (4.99 ± 0.96) × 10-13 cm3 molecule-1 s-1. The products (and molar yields) formed in the Cl-atom initiated oxidation of methyl propionate were as follows:  propionic formic anhydride (CH3CH2C(O)OC(O)H), 0.099 ± 0.019; propionic acid (CH3CH2C(O)OH), 0.139 ± 0.027; carbon monoxide, 0.132 ± 0.026; methyl pyruvate (CH3C(O)C(O)OCH3), 0.289 ± 0.057; acetaldehyde, 0.077 ± 0.015; methoxy formylperoxynitrate (CH3OC(O)O2NO2), 0.083 ± 0.016; methyl glyoxylate (H(O)CC(O)OCH3), 0.111 ± 0.022; organic nitrates, 0.07 ± 0.02; and formaldehyde. These products account for 79 ± 16% of the loss of methyl propionate. The atmospheric oxidation mechanism of methyl propionate is presented and discussed.
    The Journal of Physical Chemistry A 11/2000; 104(48). DOI:10.1021/jp001702d · 2.78 Impact Factor
  • Source
    [Show abstract] [Hide abstract]
    ABSTRACT: The management of children with chronic liver disease (CLD) mandates a multidisciplinary approach. CLDs can be classified into 'potentially' curable, treatable non-curable, and end-stage diseases. Goals pertaining to the management of CLDs can be divided into prevention or minimization of progressive liver damage in curable CLD by treating the primary cause; prevention or control of complications in treatable CLD; and prediction of the outcome in end-stage CLD in order to deliver definitive therapy by surgical procedures, including liver transplantation. Curative, specific therapies aimed at the primary causes of CLDs are, if possible, best considered by a pediatric hepatologist. Medical management of CLDs in children will be reviewed in two parts, with part I (this article) specifically focusing on 'potentially' curable CLDs. Dietary modification is the cornerstone of management for galactosemia, hereditary fructose intolerance, and certain glycogen storage diseases, as well as non-alcoholic steatohepatitis. It is also essential in tyrosinemia, in addition to nitisinone [2-(nitro-4-trifluoromethylbenzoyl)-1,3-cyclohexanedione] therapy, as well as in Wilson disease along with copper-chelating agents such as D-penicillamine, triethylenetetramine dihydrochloride, and ammonium tetrathiomolybdate. Zinc and antioxidants are adjuvant drugs in Wilson disease. New advances in chronic viral hepatitis have been made with the advent of oral antivirals. In children, currently available drugs for the treatment of chronic hepatitis B virus infection are standard interferon (IFN)-α-2, pegylated IFN-α-2 (PG-IFN), and lamivudine. In adults, adefovir and entecavir have also been licensed, whereas telbivudine, emtricitabine, tenofovir disoproxil fumarate, clevudine, and thymosin α-1 are currently undergoing clinical testing. For chronic hepatitis C virus infection, the most accepted treatment is PG-IFN plus ribavirin. Corticosteroids, with or without azathioprine, remain the basic strategy for inducing remission in autoimmune hepatitis. Ciclosporin (cyclosporine) and other immune suppressants may be used for patients who do not achieve remission, or who have significant side effects, with corticosteroid/azathioprine therapy. The above therapies can prevent, or at least minimize, progression of liver damage, particularly if started early, leading to an almost normal quality of life in affected children.
    Paediatric Drugs 12/2011; 13(6):357-70. DOI:10.2165/11591610-000000000-00000 · 1.72 Impact Factor
  • [Show abstract] [Hide abstract]
    ABSTRACT: An increased abundance of runs of homozygosity (ROH) has been associated with risk for various diseases, including schizophrenia. Here we investigate the characteristics of ROH in Palau, an Oceanic population, evaluating whether these characteristics are related to risk for psychotic disorders and the nature of this association. To accomplish these aims we evaluate a sample of 203 cases with schizophrenia and related psychotic disorders—representing almost complete ascertainment of affected individuals in the population—and contrast their ROH to that of 125 subjects chosen to function as controls. While Palauan diagnosed with psychotic disorders tend to have slightly more ROH regions than controls, the distinguishing features are that they have longer ROH regions, greater total length of ROH, and their ROH tends to co-occur more often at the same locus. The nature of the sample allows us to investigate whether rare, highly penetrant recessive variants generate such case–control differences in ROH. Neither rare, highly penetrant recessive variants nor individual common variants of large effect account for a substantial proportion of risk for psychosis in Palau. These results suggest a more nuanced model for risk is required to explain patterns of ROH for this population. © 2014 Wiley Periodicals, Inc.
    American Journal of Medical Genetics Part B Neuropsychiatric Genetics 06/2014; 165(6). DOI:10.1002/ajmg.b.32255 · 3.27 Impact Factor


Available from
Nov 10, 2014