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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.

Authors :
Mattos EP
Silva AA
Magalhães JA
Leite JC
Leistner-Segal S
Gus-Kessler R
Perez JA
Vedolin LM
Torreblanca-Zanca A
Lapunzina P
Ruiz-Perez VL
Sanseverino MT
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.)

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