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.
Brunetti-Pierri
Nicola
N
Department of Pediatrics, Federico II University, Naples, Italy.
Corso
Gaetano
G
Rossi
Massimiliano
M
Ferrari
Paola
P
Balli
Fiorella
F
Rivasi
Francesco
F
Annunziata
Ida
I
Ballabio
Andrea
A
Russo
Antonio Dello
AD
Andria
Generoso
G
Parenti
Giancarlo
G
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