Prenatal diagnosis of autosomal dominant hereditary spastic paraplegia (SPG4) using direct mutation detection

TY - JOUR

T1 - Prenatal diagnosis of autosomal dominant hereditary spastic paraplegia (SPG4) using direct mutation detection

AU - Nielsen, Jørgen E

AU - Koefoed, Pernille

AU - Kjaergaard, Susanne

AU - Jensen, Lisa Neerup

AU - Nørremølle, Anne

AU - Hasholt, Lis

N1 - Keywords: Adult; Base Sequence; Chorionic Villi Sampling; Female; Genes, Dominant; Humans; Male; Molecular Sequence Data; Pedigree; Pregnancy; Pregnancy Trimester, First; Prenatal Diagnosis; Spastic Paraplegia, Hereditary

PY - 2004

Y1 - 2004

N2 - OBJECTIVE: To present a report on prenatal diagnosis using direct SPG4 gene analysis in a family with autosomal dominant hereditary spastic paraplegia (AD-HSP). METHODS: Genetic linkage and haplotype analysis were previously carried out with chromosome 2p markers. DNA was obtained from affected individuals, the affected father, the mother, and fetal DNA from an ongoing pregnancy by chorionic villus sampling (CVS) in the first trimester. The spastin gene (SPG4) was completely sequenced. RESULTS: A novel 832insGdelAA frameshift mutation, predicted to cause loss of functional protein, was identified in the affected father and in the fetal DNA. CONCLUSIONS: This is the first report on direct prenatal diagnosis of chromosome 2p-linked AD-HSP (SPG4). In addition, we report a novel SPG4-combined small insertion/deletion mutation in exon 5, which may be the first SPG4 mutational hot spot.

AB - OBJECTIVE: To present a report on prenatal diagnosis using direct SPG4 gene analysis in a family with autosomal dominant hereditary spastic paraplegia (AD-HSP). METHODS: Genetic linkage and haplotype analysis were previously carried out with chromosome 2p markers. DNA was obtained from affected individuals, the affected father, the mother, and fetal DNA from an ongoing pregnancy by chorionic villus sampling (CVS) in the first trimester. The spastin gene (SPG4) was completely sequenced. RESULTS: A novel 832insGdelAA frameshift mutation, predicted to cause loss of functional protein, was identified in the affected father and in the fetal DNA. CONCLUSIONS: This is the first report on direct prenatal diagnosis of chromosome 2p-linked AD-HSP (SPG4). In addition, we report a novel SPG4-combined small insertion/deletion mutation in exon 5, which may be the first SPG4 mutational hot spot.

U2 - 10.1002/pd.875

DO - 10.1002/pd.875

M3 - Journal article

C2 - 15164410

SN - 0197-3851

VL - 24

SP - 363

EP - 366

JO - Prenatal Diagnosis

JF - Prenatal Diagnosis

IS - 5

ER -