JOURNAL ARTICLE
RESEARCH SUPPORT, N.I.H., INTRAMURAL
RESEARCH SUPPORT, NON-U.S. GOV'T
Add like
Add dislike
Add to saved papers

Abnormal sterol metabolism in holoprosencephaly: studies in cultured lymphoblasts.

BACKGROUND: Holoprosencephaly (HPE) is the most common structural malformation of the developing forebrain in humans. The aetiology is heterogeneous and remains unexplained in approximately 75% of patients.

OBJECTIVE: To examine cholesterol biosynthesis in lymphoblastoid cell lines of 228 patients with HPE, since perturbations of cholesterol homeostasis are an important model system to study HPE pathogenesis in animals.

METHODS: An in vitro loading test that clearly identifies abnormal increase of C27 sterols in lymphoblast-derived cells was developed using [2-(14)C] acetate as substrate.

RESULTS: 22 (9.6%) HPE cell lines had abnormal sterol pattern in the in vitro loading test. In one previously reported patient, Smith-Lemli-Opitz syndrome was diagnosed, whereas others also had clearly reduced cholesterol biosynthesis of uncertain cause. The mean (SD) cholesterol levels were 57% (15.3%) and 82% (4.7%) of total sterols in these cell lines and controls, respectively. The pattern of accumulating sterols was different from known defects of cholesterol biosynthesis. In six patients with abnormal lymphoblast cholesterol metabolism, additional mutations in genes known to be associated with HPE or chromosomal abnormalities were observed.

CONCLUSIONS: Impaired cholesterol biosynthesis may be a contributing factor in the cause of HPE and should be considered in the evaluation of causes of HPE, even if mutations in HPE-associated genes have already been found.

Full text links

We have located links that may give you full text access.
Can't access the paper?
Try logging in through your university/institutional subscription. For a smoother one-click institutional access experience, please use our mobile app.

For the best experience, use the Read mobile app

Mobile app image

Get seemless 1-tap access through your institution/university

For the best experience, use the Read mobile app

All material on this website is protected by copyright, Copyright © 1994-2024 by WebMD LLC.
This website also contains material copyrighted by 3rd parties.

By using this service, you agree to our terms of use and privacy policy.

Your Privacy Choices Toggle icon

You can now claim free CME credits for this literature searchClaim now

Get seemless 1-tap access through your institution/university

For the best experience, use the Read mobile app