Chromosomal mosaicism mitigates stigmata and cardiovascular risk factors in Turner syndrome.
OBJECTIVE
To study genotype-phenotype correlations in Turner syndrome (TS) regarding body composition, cardiovascular risk factors, stigmata and age at diagnosis vs. degree of mosaicism estimated as the percentage of 45,X and 46,XX cells.


METHODS
One hundred and twenty-six TS women, mean age 31 years, were examined by three specialists, who reported stigmata independent of each other. Dual energy X-ray absorptiometry (DXA) was used to measure bone mineral density (BMD). The karyotype was blinded. Fluorescence in situ hybridization (FISH) was performed on buccal cells. A random population sample served as controls.


RESULTS
Forty-four per cent exhibited a 45,X karyotype and 56% a second-cell line, while 27% of all had a 45,X/46,XX mosaicism. Five 45,X cases with a conventional karyotype were 45,X/46,XX mosaic according to FISH. At diagnosis, 45,X cases were younger (P < 0.05) and had more stigmata per person (P < 0.01) than the mosaics. TS with marker chromosome X or Y, iso or ring, did not differ from 45,X in this aspect. The mosaics had higher BMD and SHBG and lower total cholesterol and FSH than TS with 45,X and did not differ compared with controls in terms of body mass index (BMI), waist/hip ratio, BMD, blood pressure, cholesterol, triglycerides, SHBG, diabetes or osteoporosis. The number of stigmata correlated positively to BMI, waist/hip ratio, cholesterol and %45,X and inversely to height and %46,XX according to FISH.


CONCLUSIONS
Mosaicism seems to mitigate the TS phenotype and the cardiovascular risk factor profile. Mosaics were diagnosed 8 years later than 45,X cases. This emphasizes the necessity for a stricter genotype categorization not only in the clinic but also in research on TS than previously adopted.
El-Mansoury
Mostafa
M
Department of Internal Medicine, Sahlgrenska University Hospital/Ostra, Göteborg, Sweden.
Barrenäs
Marie-Louise
ML
Bryman
Inger
I
Hanson
Charles
C
Larsson
Christina
C
Wilhelmsen
Lars
L
Landin-Wilhelmsen
Kerstin
K
D000328:Adult; D015992:Body Mass Index; D015519:Bone Density; D002318:Cardiovascular Diseases / Q000209:etiology / Q000235:genetics*; D016022:Case-Control Studies; D016009:Chi-Square Distribution; D002784:Cholesterol / Q000097:blood; D005260:Female; D005640:Follicle Stimulating Hormone / Q000097:blood; D005838:Genotype; D006801:Humans; D017404:In Situ Hybridization, Fluorescence; D007621:Karyotyping; D009006:Monosomy; D009030:Mosaicism; D010641:Phenotype; D012306:Risk; D012738:Sex Hormone-Binding Globulin / Q000032:analysis; D014424:Turner Syndrome / Q000150:complications / Q000235:genetics*; D049629:Waist-Hip Ratio
D012738:Sex Hormone-Binding Globulin; D005640:Follicle Stimulating Hormone; D002784:Cholesterol