Abstract
Phosphoglucomutase 1 (PGM1) deficiency is a recently defined disease characterized by glycogenosis and a congenital glycosylation disorder caused by recessive mutations in the PGM1gene. We report a case of a 12-year-old boy with first-cousin parents who was diagnosed with a PGM1 deficiency due to significantly decreased PGM1 activity in his muscle. However, Sanger sequencing revealed no pathogenic mutation in the PGM1 gene in this patient. As this case presented with a cleft palate in addition to hypoglycemia and elevated transaminases and creatine kinase, karyotyping was performed and identified homozygous inv(1)(p31.1p32.3). Based on the chromosomal location of the PGM1 gene at 1p31, we analyzed the breakpoint of the inversion. Fluorescence in situ hybridization (FISH) combined with long PCR analysis revealed that the inversion disrupts the PGM1 gene within intron 1. Since the initiation codon in thePGM1 gene is located within exon 1, we speculated that this inversion inactivates the PGM1 gene and was therefore responsible for the patient’s phenotype. When standard molecular testing fails to reveal a mutation despite a positive clinical and biochemical diagnosis, the presence of a gross structural variant that requires karyotypic examination must be considered.
| Original language | English |
|---|---|
| Title of host publication | JIMD Reports |
| Publisher | Springer |
| Pages | 85-90 |
| Number of pages | 6 |
| DOIs | |
| Publication status | Published - 01-01-2019 |
Publication series
| Name | JIMD Reports |
|---|---|
| Volume | 43 |
| ISSN (Print) | 2192-8304 |
| ISSN (Electronic) | 2192-8312 |
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All Science Journal Classification (ASJC) codes
- Internal Medicine
- Endocrinology, Diabetes and Metabolism
- Biochemistry, Genetics and Molecular Biology (miscellaneous)
Cite this
}
Disruption of the responsible gene in a phosphoglucomutase 1 deficiency patient by homozygous chromosomal inversion. / Yokoi, Katsuyuki; Nakajima, Yoko; Oe, Tamae; Inagaki, Hidehito; Wada, Yoshinao; Fukuda, Tokiko; Sugie, Hideo; Yuasa, Isao; Ito, Tetsuya; Kurahashi, Hiroki.
JIMD Reports. Springer, 2019. p. 85-90 (JIMD Reports; Vol. 43).Research output: Chapter in Book/Report/Conference proceeding › Chapter
TY - CHAP
T1 - Disruption of the responsible gene in a phosphoglucomutase 1 deficiency patient by homozygous chromosomal inversion
AU - Yokoi, Katsuyuki
AU - Nakajima, Yoko
AU - Oe, Tamae
AU - Inagaki, Hidehito
AU - Wada, Yoshinao
AU - Fukuda, Tokiko
AU - Sugie, Hideo
AU - Yuasa, Isao
AU - Ito, Tetsuya
AU - Kurahashi, Hiroki
PY - 2019/1/1
Y1 - 2019/1/1
N2 - Phosphoglucomutase 1 (PGM1) deficiency is a recently defined disease characterized by glycogenosis and a congenital glycosylation disorder caused by recessive mutations in the PGM1gene. We report a case of a 12-year-old boy with first-cousin parents who was diagnosed with a PGM1 deficiency due to significantly decreased PGM1 activity in his muscle. However, Sanger sequencing revealed no pathogenic mutation in the PGM1 gene in this patient. As this case presented with a cleft palate in addition to hypoglycemia and elevated transaminases and creatine kinase, karyotyping was performed and identified homozygous inv(1)(p31.1p32.3). Based on the chromosomal location of the PGM1 gene at 1p31, we analyzed the breakpoint of the inversion. Fluorescence in situ hybridization (FISH) combined with long PCR analysis revealed that the inversion disrupts the PGM1 gene within intron 1. Since the initiation codon in thePGM1 gene is located within exon 1, we speculated that this inversion inactivates the PGM1 gene and was therefore responsible for the patient’s phenotype. When standard molecular testing fails to reveal a mutation despite a positive clinical and biochemical diagnosis, the presence of a gross structural variant that requires karyotypic examination must be considered.
AB - Phosphoglucomutase 1 (PGM1) deficiency is a recently defined disease characterized by glycogenosis and a congenital glycosylation disorder caused by recessive mutations in the PGM1gene. We report a case of a 12-year-old boy with first-cousin parents who was diagnosed with a PGM1 deficiency due to significantly decreased PGM1 activity in his muscle. However, Sanger sequencing revealed no pathogenic mutation in the PGM1 gene in this patient. As this case presented with a cleft palate in addition to hypoglycemia and elevated transaminases and creatine kinase, karyotyping was performed and identified homozygous inv(1)(p31.1p32.3). Based on the chromosomal location of the PGM1 gene at 1p31, we analyzed the breakpoint of the inversion. Fluorescence in situ hybridization (FISH) combined with long PCR analysis revealed that the inversion disrupts the PGM1 gene within intron 1. Since the initiation codon in thePGM1 gene is located within exon 1, we speculated that this inversion inactivates the PGM1 gene and was therefore responsible for the patient’s phenotype. When standard molecular testing fails to reveal a mutation despite a positive clinical and biochemical diagnosis, the presence of a gross structural variant that requires karyotypic examination must be considered.
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U2 - 10.1007/8904_2018_108
DO - 10.1007/8904_2018_108
M3 - Chapter
T3 - JIMD Reports
SP - 85
EP - 90
BT - JIMD Reports
PB - Springer
ER -