GM17424

GM17424 Fibroblast

Description:

XERODERMA PIGMENTOSUM, COMPLEMENTATION GROUP D; XPD
TRICHOTHIODYSTROPHY; TTD ICHTHYOSIFORM ERYTHRODERMA WITH HAIR ABNORMALITY AND MENTAL AND GROWTH RETARDATION, INCLUDED
EXCISION-REPAIR, COMPLEMENTING DEFECTIVE, IN CHINESE HAMSTER, 2; ERCC2

Affected:

Yes

Sex:

Female

Age:

2 YR (At Sampling)

Overview

Repository

NIGMS Human Genetic Cell Repository

Subcollection

Heritable Diseases

Class

Disorders of Nucleotide and Nucleic Acid Metabolism

Class

Repair Defective and Chromosomal Instability Syndromes

Cell Type

Fibroblast

Tissue Type

Skin

Transformant

Untransformed

Race

White

Relation to Proband

proband

Confirmation

Molecular characterization before cell line submission to CCR

Species

Homo sapiens

Common Name

Human

Remarks

Clinically affected; born at 37 weeks gestation; birth weight = 2,140 g; birth length = 44 cm; feeding problems and poor weight gain in first few months of life; hospitalized for pneumonia at ages of 8, 11, and 23 months; all scalp hair was lost within 2-10 days during pneumonia episodes but it did grow back; at age 2 years, length = 70 cm (-5 SD), weight = 6.5 kg (-4 SD), and head circumference = 42 cm (-4 SD); round face with upslanting palpebral fissures, small nose, and slightly receding chin; scalp hair sparse and brittle; nystagmus and convergent strabismus; ichthyosis diagnosed at age 2 years; mild pectus carinatum; mild psychomotor retardation; no neurological symptoms; mild photosensitivity; scanning electron microscopy on hair revealed trichorrhexis nodosa-like fractures with exposure of cortical cells; very low level of cystine in scalp hair (7.59 g nitrogen in cystine per 100 g nitrogen in all amino acids, normal index 14.23); moderate but significant deficiency of DNA repair capacity was demonstrated which appeared to be confined to 6-4 photoproducts with normal excision repair of cyclobutane pyrimidine; cell fusion studies showed that cells from donor subject belong to XP complementation group D; donor subject is a compound heterozygote: one allele has a C>T transition at nucleotide 2050 of the ERCC2/XPD gene [2050C>T] resulting in a substitution of cysteine for arginine at codon 658 [Arg658Cys (R658C)] and the other allele has a G>C transversion at nucleotide 2215 of the ERCC2/XPD gene [2215G>C] resulting in a substitution of arginine for glycine at codon 713 [Gly713Arg (G713R)].

Characterizations

Passage Frozen

IDENTIFICATION OF SPECIES OF ORIGIN

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

Gene

ERCC2

Chromosomal Location

19q13.2-q13.3

Allelic Variant 1

126340.0007; TRICHOTHIODYSTROPHY

Identified Mutation

ARG658CYS; On 1 allele of the ERCC2 gene in a girl with trichothiodystrophy (601675), Takayama et al. (Am J Hum Genet 58:263-270, 1996) found a C-to-T transition at nucleotide position 2050, resulting in an arg658-to-cys amino acid change. The causative mutation on the other allele was identified as gly713-to-arg (126340.0008). Ichthyosis and loss of scalp hair occurred intermittently in the patient.

Gene

ERCC2

Chromosomal Location

19q13.2-q13.3

Allelic Variant 2

126340.0008; TRICHOTHIODYSTROPHY

Identified Mutation

GLY713ARG; In a girl with trichothiodystrophy (601675), Takayama et al. (Am J Hum Genet 58:263-270, 1996) found a G-to-C transversion at nucleotide position 2215 of the ERCC2 gene, resulting in a gly713-to-arg amino acid substitution. They identified this mutation in compound heterozygous state with R658C (126340.0007).

Phenotypic Data

Remarks

Publications

Vermeulen W, Rademakers S, Jaspers NG, Appeldoorn E, Raams A, Klein B, Kleijer WJ, Hansen LK, Hoeijmakers JH, A temperature-sensitive disorder in basal transcription and DNA repair in humans. Nat Genet27(3):299-303 2001

PubMed ID: 11242112

Eveno E, Bourre F, Quilliet X, Chevallier-Lagente O, Roza L, Eker AP, Kleijer WJ, Nikaido O, Stefanini M, Hoeijmakers JH, et al, Different removal of ultraviolet photoproducts in genetically related xeroderma pigmentosum and trichothiodystrophy diseases. Cancer Res55(19):4325-4332 1995

PubMed ID: 7671243

Kleijer WJ, Beemer FA, Boom BW, Intermittent hair loss in a child with PIBI(D)S syndrome and trichothiodystrophy with defective DNA repair-xeroderma pigmentosum group D. Am J Med Genet52(2):227-230 1994

PubMed ID: 7802014