Investigation of the human stem cell factor KIT ligand gene, KITLG, in women with 46,XX spontaneous premature ovarian failure.
OBJECTIVE
To investigate mutations in the human KIT ligand gene (KITLG) gene as a mechanism of 46,XX spontaneous premature ovarian failure. The human KIT ligand gene, known also as human stem cell factor, is the ligand of the c-kit transmembrane tyrosine kinase receptor (KIT). This ligand-receptor interaction is known to play important roles in mouse germ cell migration and proliferation.


METHODS
Cross-sectional study.


METHODS
Clinical research center.


METHODS
Forty women with 46,XX spontaneous premature ovarian failure.


METHODS
None.


METHODS
Single-stranded conformational polymorphism analysis and DNA sequencing.


RESULTS
We found one nucleotide change of the KITLG coding region (811G-->T) that led to an alteration of the amino acid composition of the KITLG protein in one Caucasian patient (Asp210Tyr). However, we found the same alteration in two normal control Caucasian samples. Three nucleotide substitutions were found in the noncoding exon of KITLG (exon 10). We also identified two intronic polymorphisms. Thus, we did not identify a single significant mutation in the coding region of the KITLG gene in any of 40 patients (upper 95% confidence limit is 7.2%).


CONCLUSIONS
Mutations in the coding regions of the KITLG gene appear not to be a common cause of 46,XX spontaneous premature ovarian failure in North American women.
Hui
Emily S
ES
Section on Women's Health Research, Developmental Endocrinology Branch, National Institutes of Health, Bethesda, Maryland, USA.
Udofa
Ekemini A
EA
Soto
Jackeline
J
Vanderhoof
Vien H
VH
Zachman
Keith
K
Tong
Zhi-Bin
ZB
Nelson
Lawrence M
LM
D000293:Adolescent; D000328:Adult; D002869:Chromosome Aberrations; D025063:Chromosome Disorders / Q000453:epidemiology* / Q000235:genetics*; D041321:Chromosomes, Human, X / Q000235:genetics*; D004252:DNA Mutational Analysis; D005260:Female; D005819:Genetic Markers / Q000235:genetics; D020022:Genetic Predisposition to Disease / Q000453:epidemiology / Q000235:genetics; D006801:Humans; D008396:Maryland / Q000453:epidemiology; D020641:Polymorphism, Single Nucleotide; D015995:Prevalence; D016649:Primary Ovarian Insufficiency / Q000453:epidemiology* / Q000235:genetics*; D018570:Risk Assessment / Q000379:methods*; D019089:Stem Cell Factor / Q000235:genetics*
D005819:Genetic Markers; D019089:Stem Cell Factor