NA13425

NA13425 DNA from Fibroblast

Description:

EHLERS-DANLOS SYNDROME, TYPE VI
PROCOLLAGEN-LYSINE, 2-OXOGLUTARATE 5-DIOXYGENASE; PLOD1

Affected:

Yes

Sex:

Male

Age:

7 YR (At Sampling)

Overview

Repository

NIGMS Human Genetic Cell Repository

Subcollection

Heritable Diseases

Class

Disorders of Connective Tissue, Muscle, and Bone

Quantity

10 µg

Quantitation Method

Please see our FAQ

Cell Type

Fibroblast

Transformant

Untransformed

Sample Source

DNA from Fibroblast

Race

White

Family Member

Relation to Proband

proband

Confirmation

Molecular characterization before cell line submission to CCR

Species

Homo sapiens

Common Name

Human

Remarks

Mexican-American; hemifacial asymmetry & disloc of wrist & hip at birth; myopia, hyperextensible, soft & velvety skin, & hypotrophic wound healing at age 6; lysyl hydroxylase/prolyl hydroxylase is 24% of norm; donor subject is a compound heterozygote: one allele has a 3 bp deletion of the lysyl hydroxylase (PLOD1) gene that resulted in loss of residue glu532 [Glu532Del] and the second allele has a G>A change that produced a gly678-to-arg codon change in a highly conserved region of the enzyme

Characterizations

Passage Frozen

IDENTIFICATION OF SPECIES OF ORIGIN

Species of Origin Confirmed by Nucleoside Phosphorylase, Glucose-6-Phosphate Dehydrogenase, and Lactate Dehydrogenase Isoenzyme Electrophoresis

procollagen-lysine 5-dioxygenase

According to the submitter, biochemical test results for this subject showed decreased enzyme activity. EC Number: 1.14.11.4; 24% activity.

Gene

PLOD1

Chromosomal Location

1p36.3-p36.2

Allelic Variant 1

153454.0004; EHLERS-DANOLS SYNDROME TYPE VIA

Identified Mutation

3-BP DEL, GLU532DEL; Ha et al (1994) found compound heterozygosity of mutations in the PLOD gene in a male of Mexican-American ancestry born full term without premature rupture of fetal membranes to a nonconsanguineous couple. He was noted at birth to exhibit hemifacial asymmetry and dislocation of the right wrist and hip. Other features characteristic of E-D VI (225400) included myopia, hyperextensible and velvety skin, and hypotrophic wound healing. Bilateral herniorrhaphy and orchidopexy were performed at the age of 6 months, and Harrington rod placement for kyphoscoliosis at the age of 3 years. He was demonstrated to be ascorbate-responsive and did well from the age of 6 to approximately 14 years when he stopped taking ascorbate. These features were reported by Dembure et al. (1984, 1987), Elsas et al. (1978), and Miller et al. (1979). At the age of 15 years, he had spontaneous arterial rupture in the upper thigh. Bilateral venous thrombosis resulted from compression stasis which required fasciotomies. Pharmacologic amounts of ascorbate (5.0 g/d) were reinstituted and wound healing progressed normally. Amino acid analysis of the skin showed zero hydroxylysine per 1,000 residues with normal values being 5 per 1,000. Assay of lysyl hydroxylase activity in cultured dermal fibroblasts showed that the patient had a ratio of lysyl hydroxylase to prolyl hydroxylase that was 24% of the control values. An autosomal recessive mode of inheritance was deduced from the same assay performed on his parents' dermal fibroblasts, which showed 52 and 86% lysyl hydroxylase activity relative to prolyl hydroxylase activity, in the father and mother, respectively. Neither parent had clinical evidence of E-D VI. Ha et al. (1994) detected a G-to-A change that produced a gly678-to-arg codon change in a highly conserved region of the enzyme in the paternal allele of the proband. The maternal allele showed a 3-bp deletion that resulted in loss of residue glu532 (153454.0003).

Gene

PLOD1

Chromosomal Location

1p36.3-p36.2

Allelic Variant 2

153454.0003; EHLERS-DANOLS SYNDROME TYPE VIA

Identified Mutation

GLY678ARG; Ha et al (1994) found compound heterozygosity of mutations in the PLOD gene in a male of Mexican-American ancestry born full term without premature rupture of fetal membranes to a nonconsanguineous couple. He was noted at birth to exhibit hemifacial asymmetry and dislocation of the right wrist and hip. Other features characteristic of E-D VI (225400) included myopia, hyperextensible and velvety skin, and hypotrophic wound healing. Bilateral herniorrhaphy and orchidopexy were performed at the age of 6 months, and Harrington rod placement for kyphoscoliosis at the age of 3 years. He was demonstrated to be ascorbate-responsive and did well from the age of 6 to approximately 14 years when he stopped taking ascorbate. These features were reported by Dembure et al. (1984, 1987), Elsas et al. (1978), and Miller et al. (1979). At the age of 15 years, he had spontaneous arterial rupture in the upper thigh. Bilateral venous thrombosis resulted from compression stasis which required fasciotomies. Pharmacologic amounts of ascorbate (5.0 g/d) were reinstituted and wound healing progressed normally. Amino acid analysis of the skin showed zero hydroxylysine per 1,000 residues with normal values being 5 per 1,000. Assay of lysyl hydroxylase activity in cultured dermal fibroblasts showed that the patient had a ratio of lysyl hydroxylase to prolyl hydroxylase that was 24% of the control values. An autosomal recessive mode of inheritance was deduced from the same assay performed on his parents' dermal fibroblasts, which showed 52 and 86% lysyl hydroxylase activity relative to prolyl hydroxylase activity, in the father and mother, respectively. Neither parent had clinical evidence of E-D VI. Ha et al. (1994) detected a G-to-A change that produced a gly678-to-arg codon change in a highly conserved region of the enzyme in the paternal allele of the proband. The maternal allele showed a 3-bp deletion that resulted in loss of residue glu532 (153454.0003).

Phenotypic Data

Remarks

Publications

Kellogg G, Thorsson B, Cai Y, Wisotzkey R, Pollock A, Akana M, Fox R, Jansen M, Gudmundsson EF, Patel B, Chang C, Jaremko M, Puig O, Gudnason V, Emilsson V, Molecular screening of familial hypercholesterolemia in Icelanders Scandinavian journal of clinical and laboratory investigation:1-7 2020

PubMed ID: 32706999

Ha VT, Marshall MK, Elsas LJ, Pinnell SR, Yeowell HN, A patient with Ehlers-Danlos syndrome type VI is a compound heterozygote for mutations in the lysyl hydroxylase gene. J Clin Invest93:1716-21 1994

PubMed ID: 8163671

Dembure PP, Janko AR, Priest JH, Elsas LJ, Ascorbate regulation of collagen biosynthesis in Ehlers-Danlos syndrome, type VI. Metabolism36:687-91 1987

PubMed ID: 3110540

Dembure PP, Priest JH, Snoddy SC, Elsas LJ, Genotyping and prenatal assessment of collagen lysyl hydroxylase deficiency in a family with Ehlers-Danlos syndrome type VI. Am J Hum Genet36:783-90 1984

PubMed ID: 6089551