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Identification of a premature stop codon mutation in the PHGDH gene in severe Neu-Laxova syndrome-evidence for phenotypic variability.
Identification of a premature stop codon mutation in the PHGDH gene in severe Neu-Laxova syndrome-evidence for phenotypic variability.
- Source :
-
American journal of medical genetics. Part A [Am J Med Genet A] 2015 Jun; Vol. 167 (6), pp. 1323-9. Date of Electronic Publication: 2015 Apr 25. - Publication Year :
- 2015
-
Abstract
- In some cases Neu-Laxova syndrome (NLS) is linked to serine deficiency due to mutations in the phosphoglycerate dehydrogenase (PHGDH) gene. We describe the prenatal and postnatal findings in a fetus with one of the most severe NLS phenotypes described so far, caused by a homozygous nonsense mutation of PHGDH. Serial ultrasound (US) and pre- and postnatal magnetic resonance imaging (MRI) evaluations were performed. Prenatally, serial US evaluations suggested symmetric growth restriction, microcephaly, hypoplasia of the cerebellar vermis, micrognathia, hydrops, shortened limbs, arthrogryposis, and talipes equinovarus. The prenatal MRI confirmed these findings prompting a diagnosis of NLS. After birth, radiological imaging did not detect any gross bone abnormalities. DNA was extracted from fetal and parental peripheral blood, all coding exons of PHGDH were PCR-amplified and subjected to Sanger sequencing. Sequencing of PHGDH identified a homozygous premature stop codon mutation (c.1297C>T; p.Gln433*) in fetal DNA, both parents (first-cousins) being heterozygotes. Based on previous associations of mutations in this gene with a milder NLS phenotype, as well as cases of serine deficiency, these observations lend further support to a genotype-phenotype correlation between the degree of PHGDH inactivation and disease severity.<br /> (© 2015 Wiley Periodicals, Inc.)
- Subjects :
- Abnormalities, Multiple diagnosis
Abnormalities, Multiple pathology
Base Sequence
Brain Diseases diagnosis
Brain Diseases pathology
Carbohydrate Metabolism, Inborn Errors diagnosis
Carbohydrate Metabolism, Inborn Errors pathology
Consanguinity
Female
Fetal Growth Retardation diagnosis
Fetal Growth Retardation pathology
Fetus
Gene Expression
Genes, Lethal
Genetic Variation
Genotype
Homozygote
Humans
Ichthyosis diagnosis
Ichthyosis pathology
Infant, Newborn
Limb Deformities, Congenital diagnosis
Limb Deformities, Congenital pathology
Male
Microcephaly diagnosis
Microcephaly pathology
Molecular Sequence Data
Pedigree
Psychomotor Disorders diagnosis
Psychomotor Disorders pathology
Seizures diagnosis
Seizures pathology
Sequence Analysis, DNA
Severity of Illness Index
Ultrasonography, Prenatal
Abnormalities, Multiple genetics
Brain Diseases genetics
Carbohydrate Metabolism, Inborn Errors genetics
Codon, Nonsense
Fetal Growth Retardation genetics
Ichthyosis genetics
Limb Deformities, Congenital genetics
Microcephaly genetics
Phenotype
Phosphoglycerate Dehydrogenase deficiency
Phosphoglycerate Dehydrogenase genetics
Psychomotor Disorders genetics
Seizures genetics
Subjects
Details
- Language :
- English
- ISSN :
- 1552-4833
- Volume :
- 167
- Issue :
- 6
- Database :
- MEDLINE
- Journal :
- American journal of medical genetics. Part A
- Publication Type :
- Academic Journal
- Accession number :
- 25913727
- Full Text :
- https://doi.org/10.1002/ajmg.a.36930