Diagnosis of Smith-Lemli-Opitz syndrome by ultraviolet spectrophotometry

Scalco, Fernanda B.; Cruzes, Vania M.; Vendramini, Regina Célia; Brunetti, Iguatemy Lourenço; Moretti-Ferreira, Danilo

doi:10.1590/s0100-879x2003001000008

Cited by 2 publications

(1 citation statement)

References 21 publications

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“…DNA sequencing of the 12 exons with flanking intron sequences of the PCSK9 gene was performed on the proband and his parents according to Leren 2004. The level of 7‐dehydrocholesterol was determined by UV spectrophotometry [Scalco et al, 2003].…”

Section: Methodsmentioning

confidence: 99%

Deletion (1)(p32.2–p32.3) detected by array‐CGH in a patient with developmental delay/mental retardation, dysmorphic features and low cholesterol: A new microdeletion syndrome?

Mulatinho

Llerena

Leren

et al. 2008

American J of Med Genetics Pt A

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We report on a 25-year-old male with mental retardation and global developmental delay, low levels of total and LDL cholesterol and dysmorphism, which includes macrocephaly, hypertelorism, synophrys, telecanthus, prominent philtrum, low set ears, bilateral cataracts, bilateral cleft lip with cleft palate and widely spaced nipples. While his karyotype and subtelomeric FISH studies were normal, a de novo, 5.4 Mb interstitial deletion at 1p32 [del(1)(p32.2-p32.3)] was identified by oligonucleotide aCGH. The deleted region encompasses a cluster of genes involved in fatty acid oxidation and cholesterol metabolism. One of these genes is PCSK9, a key regulator for a number of cell-surface LDL receptors. In addition to the loss of the paternal allele, our patient is hemizygous for the A443T weak loss-of-function mutation in exon 8 of PCSK9. Loss-of-function mutations within PCSK9 have been shown to cause hypocholesterolemia. Another gene also mapped to this region and deleted in this patient is DAB1, reported to be involved in brain development. Based on the findings in the current patient and in the four previously reported individuals with del(1)(p32.2-p32.3), we suggest that these patients may have a new microdeletion syndrome that may have gone undetected because of its location in a G-negative band. However, the condition can easily be identified by array-CGH.

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Section: Methodsmentioning

confidence: 99%

Deletion (1)(p32.2–p32.3) detected by array‐CGH in a patient with developmental delay/mental retardation, dysmorphic features and low cholesterol: A new microdeletion syndrome?

Mulatinho

Llerena

Leren

et al. 2008

American J of Med Genetics Pt A

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Signaling by the human serotonin1A receptor is impaired in cellular model of Smith–Lemli–Opitz Syndrome

Paila

Murty

Vairamani

et al. 2008

Biochimica et Biophysica Acta (BBA) - Biomembranes

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The Smith-Lemli-Opitz Syndrome (SLOS) is a congenital and developmental malformation syndrome associated with defective cholesterol biosynthesis. SLOS is clinically diagnosed by reduced plasma levels of cholesterol along with elevated levels of 7-dehydrocholesterol (and its positional isomer 8-dehydrocholesterol) and the ratio of their concentrations to that of cholesterol. Since SLOS is associated with neurological deformities and malfunction, exploring the function of neuronal receptors and their interaction with membrane cholesterol under these conditions assumes significance. We have earlier shown the requirement of membrane cholesterol for the ligand binding function of an important neurotransmitter G-protein coupled receptor, the serotonin(1A) receptor. In the present work, we have generated a cellular model of SLOS using CHO cells stably expressing the human serotonin(1A) receptor. This was achieved by metabolically inhibiting the biosynthesis of cholesterol, utilizing a specific inhibitor (AY 9944) of the enzyme required in the final step of cholesterol biosynthesis. We utilized this cellular model to monitor the function of the human serotonin(1A) receptor under SLOS-like condition. Our results show that ligand binding activity, G-protein coupling and downstream signaling of serotonin(1A) receptors are impaired in SLOS-like condition, although the membrane receptor level does not exhibit any reduction. Importantly, metabolic replenishment of cholesterol using serum partially restored the ligand binding activity of the serotonin(1A) receptor. These results are potentially useful in developing strategies for the future treatment of the disease since intake of dietary cholesterol is the only feasible treatment for SLOS patients.

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Diagnosis of Smith-Lemli-Opitz syndrome by ultraviolet spectrophotometry

Cited by 2 publications

References 21 publications

Deletion (1)(p32.2–p32.3) detected by array‐CGH in a patient with developmental delay/mental retardation, dysmorphic features and low cholesterol: A new microdeletion syndrome?

Deletion (1)(p32.2–p32.3) detected by array‐CGH in a patient with developmental delay/mental retardation, dysmorphic features and low cholesterol: A new microdeletion syndrome?

Signaling by the human serotonin1A receptor is impaired in cellular model of Smith–Lemli–Opitz Syndrome

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