Genetic and functional studies reveal a novel noncoding variant in GALT associated with a false positive newborn screening result for galactosemia

Ying Liu; Alpa Sidhu; Lora H Bean; Robert L Conway; Judith L Fridovich-Keil

doi:10.1016/j.cca.2015.04.030

Back

Genetic and functional studies reveal a novel noncoding variant in GALT associated with a false positive newborn screening result for galactosemia

Journal article

Open access

Peer reviewed

Genetic and functional studies reveal a novel noncoding variant in GALT associated with a false positive newborn screening result for galactosemia

Ying Liu, Alpa Sidhu, Lora H Bean, Robert L Conway and Judith L Fridovich-Keil

Clinica chimica acta, Vol.446, pp.171-174

06/15/2015

DOI: 10.1016/j.cca.2015.04.030

PMCID: PMC4449829

PMID: 25920691

Files and links (1)

url

https://doi.org/10.1016/j.cca.2015.04.030View

Published (Version of record) Open Access

Abstract

Classic galactosemia (CG) is a potentially lethal genetic disorder that results from profound loss of galactose-1-phosphate uridylyltransferase (GALT). CG is detected by newborn screening (NBS) in many countries; however, conclusive diagnosis can be complex due to broad and overlapping ranges of GALT activity. Molecular studies can also be complex due to allelic heterogeneity at the GALT locus. We conducted both biochemical and molecular follow-up studies for an infant flagged by NBS for possible galactosemia. To clarify the diagnosis we also conducted biochemical and RNA studies of lymphoblasts prepared from the child and one parent. We identified a novel noncoding GALT variant, c.377+17C>T, that was homozygous in the child and heterozygous in both parents. The child and both parents also showed diminished GALT activity in red blood cells, and transformed lymphoblasts from the child and one parent further showed diminished GALT activity. However, qRT-PCR studies demonstrated apparently normal GALT mRNA levels in lymphoblasts, and Gal-1P values measured in the child following galactose exposure in infancy and at 1 year were normal. These results highlight the existence of rare but apparently benign variants in GALT and underscore the need for functional studies to distinguish pathogenic from benign variants.

Gene Expression

Mutation

Genetic Testing

UTP-Hexose-1-Phosphate Uridylyltransferase - genetics

Herpesvirus 4, Human - growth & development

Humans

Male

Asymptomatic Diseases

Genetic Loci

Neonatal Screening

Galactosemias - genetics

Lymphocytes - virology

Adult

Female

Galactosephosphates - metabolism

Infant, Newborn

Lymphocytes - metabolism

Transformation, Genetic

Galactosemias - diagnosis

Cells, Cultured

Galactosemias - blood

Homozygote

UTP-Hexose-1-Phosphate Uridylyltransferase - deficiency

Heterozygote

Consanguinity

Details

Title: Subtitle: Genetic and functional studies reveal a novel noncoding variant in GALT associated with a false positive newborn screening result for galactosemia
Creators: Ying Liu - Department of Human Genetics, Emory University School of Medicine, Atlanta, GA 30322, USA
Alpa Sidhu - Children's Hospital of Michigan Metabolic Clinic, Wayne State University, Detroit, MI 48201, USA
Lora H Bean - Department of Human Genetics, Emory University School of Medicine, Atlanta, GA 30322, USA
Robert L Conway - Children's Hospital of Michigan Metabolic Clinic, Wayne State University, Detroit, MI 48201, USA
Judith L Fridovich-Keil - Department of Human Genetics, Emory University School of Medicine, Atlanta, GA 30322, USA. Electronic address: jfridov@emory.edu
Resource Type: Journal article
Publication Details: Clinica chimica acta, Vol.446, pp.171-174
DOI: 10.1016/j.cca.2015.04.030
PMID: 25920691
PMCID: PMC4449829
NLM abbreviation: Clin Chim Acta
ISSN: 0009-8981
eISSN: 1873-3492
Grant note: R01DK059904 / NIDDK NIH HHS R01 DK059904 / NIDDK NIH HHS
Language: English
Date published: 06/15/2015
Academic Unit: Stead Family Department of Pediatrics; Medical Genetics and Genomics
Record Identifier: 9984093350302771

Metrics

24 Record Views

2 Times Cited - Web of Science