Donor splice site mutation in intron 5 of theHEXA gene in a Turkish infant with Tay-Sachs disease

Özkara, Hatice Asuman; Akerman, Beverly R.; Ciliv, G; Topçu, Meral; Renda, Yavuz; Gravel, R.A.

doi:10.1002/humu.1380050216

Cited by 15 publications

(2 citation statements)

References 15 publications

(14 reference statements)

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“…23 In this study, DNA analysis was not performed for confirmation of the disease since many novel mutations are being described in the Turkish population and molecular heterogeneity is found to be common for certain diseases such as Tay-Sachs disease, GM1 gangliosidosis, MLD, and Fabry disease. [32][33][34][35][36] As a result, the molecular basis of the LSDs may be evaluated as heterogeneous in Turkey and DNA analysis is not feasible for each patient. Prenatal enzymatic diagnosis is a reliable and easy way to prevent the grave outcomes in infants with LSDs.…”

Section: Discussionmentioning

confidence: 99%

Prenatal enzymatic diagnosis of lysosomal storage diseases using cultured amniotic cells, uncultured chorionic villus samples, and fetal blood cells: Hacettepe experience

et al. 2019

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Aim To evaluate the results of prenatal enzymatic diagnostic studies for detecting lysosomal storage diseases (LSDs) during 1992 to 2018. Methods Pregnancies subjected to “prenatal enzymatic diagnosis of LSDs” during 1992 to 2018 were retrospectively evaluated in terms of invasive prenatal tests, type of LSDs, and obstetric outcomes. Results A total of 142 pregnancies were evaluated for various types of LSDs of which 30, 103, and 9 cases were subjected to amniocentesis, chorionic villus sampling, and fetal blood sampling, respectively. Retrospective analysis of prenatal diagnosis revealed that LSDs affected 33% (47/142) of the fetuses. Sandhoff disease (28%), Tay‐Sachs disease (27%), and metachromatic leukodystrophy (MLD) (20%) were the most frequent LSDs among the evaluated cases with two false negatives, one each for Tay‐Sachs disease and MLD. Conclusion Enzymatic prenatal diagnoses of certain LSDs may serve as a primary intervention point for families with index cases of infantile or late infantile types of LSDs, since they are associated with poor outcomes, including mortality. In addition, enzyme studies alone may also be feasible for populations with increased risk of molecular heterogeneity, novel mutations, and low‐income settings where genetic analysis is inaccessible.

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Section: Discussionmentioning

confidence: 99%

Prenatal enzymatic diagnosis of lysosomal storage diseases using cultured amniotic cells, uncultured chorionic villus samples, and fetal blood cells: Hacettepe experience

et al. 2019

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“…To date, more than 90 different mutations in the Hex A gene have been identified in Tay‐Sachs patients, of which five were found in Turkish populations 1,7,8 …”

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confidence: 99%

Biochemical and molecular characterization of mutant hexosaminidase A in a Turkish family

Sinici¹,

Özkara²,

Topçu

et al. 2003

Pediatrics International

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The 12-bp deletion mutation in exon 10 of Hex A is responsible for the increased thermostability of the enzyme. Considering this mutation has previously been found in a Turkish Tay-Sachs patient, the patient in the present study may have another mutation on the Hex B gene that causes decreased thermostability of the enzyme. Thermal inactivation assay may not be sufficient for a correct diagnosis in such unusual cases.

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Tay-Sachs disease-causing mutations and neutral polymorphisms in the Hex A gene

Myerowitz

1997

Hum. Mutat.

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Tay-Sachs disease is an autosomal recessive disorder affecting the central nervous system. The disorder results from mutations in the gene encoding the ~-subunit of Ä-hexosaminidase A, a lysosomal enzyme composed of ~ and Ä polypeptides. Seventy-eight mutations in the Hex A gene have been described and include 65 single base substitutions, one large and 10 small deletions, and two small insertions. Because these mutations cripple the catalytic activity of Ä-hexosaminidase to varying degrees, Tay-Sachs disease displays clinical heterogeneity. Forty-five of the single base substitutions cause missense mutations; 39 of these are disease causing, three are benign but cause a change in phenotype, and three are neutral polymorphisms. Six nonsense mutations and 14 splice site lesions result from single base substitutions, and all but one of the splice site lesions cause a severe form of Tay-Sachs disease. Eight frameshift mutations arise from six deletion-and two insertion-type lesions. One of these insertions, consisting of four bases within exon 11, is found in 80% of the carriers of Tay-Sachs disease from the Ashkenazi Jewish population, an ethnic group that has a 10-fold higher gene frequency for a severe form of the disorder than the general population. A very large deletion, 7.5 kilobases, including all of exon 1 and portions of DNA upstream and downstream from that exon, is the major mutation found in Tay-Sachs disease carriers from the French Canadian population, a geographic isolate displaying an elevated carrier frequency. Most of the other mutations are confined to single pedigrees. Identification of these mutations has permitted more accurate carrier information, prenatal diagnosis, and disease prognosis. In conjunction with a precise tertiary structure of the enzyme, these mutations could be used to pin insight into the structure-function relationships of the lysosomal enzyme.

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Donor splice site mutation in intron 5 of theHEXA gene in a Turkish infant with Tay-Sachs disease

Cited by 15 publications

References 15 publications

Prenatal enzymatic diagnosis of lysosomal storage diseases using cultured amniotic cells, uncultured chorionic villus samples, and fetal blood cells: Hacettepe experience

Prenatal enzymatic diagnosis of lysosomal storage diseases using cultured amniotic cells, uncultured chorionic villus samples, and fetal blood cells: Hacettepe experience

Biochemical and molecular characterization of mutant hexosaminidase A in a Turkish family

Tay-Sachs disease-causing mutations and neutral polymorphisms in the Hex A gene

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