Lathosterolosis, a novel multiple-malformation/mental retardation syndrome due to deficiency of 3beta-hydroxysteroid-delta5-desaturase.
We report the clinical, biochemical, and molecular characterization of a patient with a novel defect of cholesterol biosynthesis. This patient presented with a complex phenotype, including multiple congenital anomalies, mental retardation, and liver disease. In the patient's plasma and cells, we found increased levels of lathosterol. The biosynthesis of cholesterol in the patient's fibroblasts was defective, showing a block in the conversion of lathosterol into 7-dehydrocholesterol. The activity of 3beta-hydroxysteroid-Delta(5)-desaturase (SC5D), the enzyme involved in this reaction, was deficient in the patient's fibroblasts. Sequence analysis of the SC5D gene in the patient's DNA, showing the presence of two missense mutations (R29Q and G211D), confirmed that the patient is affected by a novel defect of cholesterol biosynthesis.
Department of Pediatrics, Federico II University, Naples, Italy.
Nicola
N
Brunetti-Pierri
Gaetano
G
Corso
Massimiliano
M
Rossi
Paola
P
Ferrari
Fiorella
F
Balli
Francesco
F
Rivasi
Ida
I
Annunziata
Andrea
A
Ballabio
Antonio Dello
AD
Russo
Generoso
G
Andria
Giancarlo
G
Parenti
D000015:Abnormalities, Multiple / Q000201:enzymology* / Q000378:metabolism; D002784:Cholesterol / Q000378:metabolism*; D006801:Humans; D007223:Infant; D008607:Intellectual Disability / Q000201:enzymology* / Q000378:metabolism; D010088:Oxidoreductases / Q000172:deficiency / Q000235:genetics / Q000378:metabolism*; D044925:Oxidoreductases Acting on CH-CH Group Donors; D013577:Syndrome
C033144:lathosterol delta-5-dehydrogenase; C001521:lathosterol; D002784:Cholesterol; D010088:Oxidoreductases; D044925:Oxidoreductases Acting on CH-CH Group Donors