Novel Mutation in the Feline <i>GAA</i> Gene in a Cat with Glycogen Storage Disease Type II (Pompe Disease)
Glycogen storage disease type II (Pompe disease: PD) is an autosomal recessively inherited fatal genetic disorder that results from the deficiency of a glycogen hydrolyzing enzyme, acid α-glucosidase encoded by the <i>GAA</i> gene. Here, we describe the molecular basis of genetic defects...
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MDPI AG
2023-04-01
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| author | Tofazzal Md Rakib Md Shafiqul Islam Shigeki Tanaka Akira Yabuki Shahnaj Pervin Shinichiro Maki Abdullah Al Faruq Martia Rani Tacharina Osamu Yamato |
| author_facet | Tofazzal Md Rakib Md Shafiqul Islam Shigeki Tanaka Akira Yabuki Shahnaj Pervin Shinichiro Maki Abdullah Al Faruq Martia Rani Tacharina Osamu Yamato |
| author_sort | Tofazzal Md Rakib |
| collection | DOAJ |
| description | Glycogen storage disease type II (Pompe disease: PD) is an autosomal recessively inherited fatal genetic disorder that results from the deficiency of a glycogen hydrolyzing enzyme, acid α-glucosidase encoded by the <i>GAA</i> gene. Here, we describe the molecular basis of genetic defects in an 8-month-old domestic short-haired cat with PD. The cat was previously diagnosed with PD based on the clinical and pathological findings of hypertrophic cardiomyopathy and excessive accumulation of glycogen in the cardiac muscles. Sanger sequencing was performed on 20 exons of the feline <i>GAA</i> gene using genomic DNA extracted from paraffin-embedded liver tissues. The affected cat was found to be homozygous for the <i>GAA</i>:c.1799G>A mutation resulting in an amino acid substitution (p.R600H) of acid α-glucosidase, a codon position of which is identical with three missense mutations (p.R600C, p.R600L, and p.R600H) causing human infantile-onset PD (IOPD). Several stability and pathogenicity predictors have also shown that the feline mutation is deleterious and severely decreases the stability of the GAA protein. The clinical, pathological, and molecular findings in the cat were similar to those of IOPD in humans. To our knowledge, this is the first report of a pathogenic mutation in a cat. Feline PD is an excellent model for human PD, especially IOPD. |
| first_indexed | 2024-03-11T05:19:01Z |
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| id | doaj.art-8141baeef4014d0381d2b05aaa20e62b |
| institution | Directory Open Access Journal |
| issn | 2076-2615 |
| language | English |
| last_indexed | 2024-03-11T05:19:01Z |
| publishDate | 2023-04-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | Animals |
| spelling | doaj.art-8141baeef4014d0381d2b05aaa20e62b2023-11-17T18:00:21ZengMDPI AGAnimals2076-26152023-04-01138133610.3390/ani13081336Novel Mutation in the Feline <i>GAA</i> Gene in a Cat with Glycogen Storage Disease Type II (Pompe Disease)Tofazzal Md Rakib0Md Shafiqul Islam1Shigeki Tanaka2Akira Yabuki3Shahnaj Pervin4Shinichiro Maki5Abdullah Al Faruq6Martia Rani Tacharina7Osamu Yamato8Laboratory of Clinical Pathology, Joint Faculty of Veterinary Medicine, Kagoshima University, Kagoshima 890-0065, JapanLaboratory of Clinical Pathology, Joint Faculty of Veterinary Medicine, Kagoshima University, Kagoshima 890-0065, JapanAlpha Animal Hospital, Kawanakajima, Nagano 381-2226, JapanLaboratory of Clinical Pathology, Joint Faculty of Veterinary Medicine, Kagoshima University, Kagoshima 890-0065, JapanLaboratory of Clinical Pathology, Joint Faculty of Veterinary Medicine, Kagoshima University, Kagoshima 890-0065, JapanLaboratory of Clinical Pathology, Joint Faculty of Veterinary Medicine, Kagoshima University, Kagoshima 890-0065, JapanLaboratory of Clinical Pathology, Joint Faculty of Veterinary Medicine, Kagoshima University, Kagoshima 890-0065, JapanLaboratory of Clinical Pathology, Joint Faculty of Veterinary Medicine, Kagoshima University, Kagoshima 890-0065, JapanLaboratory of Clinical Pathology, Joint Faculty of Veterinary Medicine, Kagoshima University, Kagoshima 890-0065, JapanGlycogen storage disease type II (Pompe disease: PD) is an autosomal recessively inherited fatal genetic disorder that results from the deficiency of a glycogen hydrolyzing enzyme, acid α-glucosidase encoded by the <i>GAA</i> gene. Here, we describe the molecular basis of genetic defects in an 8-month-old domestic short-haired cat with PD. The cat was previously diagnosed with PD based on the clinical and pathological findings of hypertrophic cardiomyopathy and excessive accumulation of glycogen in the cardiac muscles. Sanger sequencing was performed on 20 exons of the feline <i>GAA</i> gene using genomic DNA extracted from paraffin-embedded liver tissues. The affected cat was found to be homozygous for the <i>GAA</i>:c.1799G>A mutation resulting in an amino acid substitution (p.R600H) of acid α-glucosidase, a codon position of which is identical with three missense mutations (p.R600C, p.R600L, and p.R600H) causing human infantile-onset PD (IOPD). Several stability and pathogenicity predictors have also shown that the feline mutation is deleterious and severely decreases the stability of the GAA protein. The clinical, pathological, and molecular findings in the cat were similar to those of IOPD in humans. To our knowledge, this is the first report of a pathogenic mutation in a cat. Feline PD is an excellent model for human PD, especially IOPD.https://www.mdpi.com/2076-2615/13/8/1336Pompe disease<i>GAA</i> genelysosomal diseaseglycogen storage disease type IIcat |
| spellingShingle | Tofazzal Md Rakib Md Shafiqul Islam Shigeki Tanaka Akira Yabuki Shahnaj Pervin Shinichiro Maki Abdullah Al Faruq Martia Rani Tacharina Osamu Yamato Novel Mutation in the Feline <i>GAA</i> Gene in a Cat with Glycogen Storage Disease Type II (Pompe Disease) Animals Pompe disease <i>GAA</i> gene lysosomal disease glycogen storage disease type II cat |
| title | Novel Mutation in the Feline <i>GAA</i> Gene in a Cat with Glycogen Storage Disease Type II (Pompe Disease) |
| title_full | Novel Mutation in the Feline <i>GAA</i> Gene in a Cat with Glycogen Storage Disease Type II (Pompe Disease) |
| title_fullStr | Novel Mutation in the Feline <i>GAA</i> Gene in a Cat with Glycogen Storage Disease Type II (Pompe Disease) |
| title_full_unstemmed | Novel Mutation in the Feline <i>GAA</i> Gene in a Cat with Glycogen Storage Disease Type II (Pompe Disease) |
| title_short | Novel Mutation in the Feline <i>GAA</i> Gene in a Cat with Glycogen Storage Disease Type II (Pompe Disease) |
| title_sort | novel mutation in the feline i gaa i gene in a cat with glycogen storage disease type ii pompe disease |
| topic | Pompe disease <i>GAA</i> gene lysosomal disease glycogen storage disease type II cat |
| url | https://www.mdpi.com/2076-2615/13/8/1336 |
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