title: A novel frameshift mutation in the sterol 27-hydroxylase gene in an Egyptian family with cerebrotendinous xanthomatosis without cataract.
abstract: Cerebrotendinous xanthomatosis (CTX) is a rare autosomal recessive lipid storage disorder caused by deficiency of the mitochondrial cytochrome P450 sterol 27-hydroxylase enzyme encoded by CYP27A1 gene. CTX is characterized by tendon xanthomas, juvenile cataracts and multiple progressive neurological symptoms. Here we report on the clinical and molecular findings of a 35-years old Egyptian patient with CTX without cataract. Parents were first cousins with family history of two deceased sibs with mild impaired cognitive functions and epilepsy without appearance of tendon xanthomas. Our proband had learning disabilities and developed seizures at 9 years old. Tendon xanthomata appeared at the age of 16 and his neurological symptoms remained stationary till 28 years followed by progressive cerebello-pyramidal signs, dementia and psychiatric disturbance. Cataract was not evident in our patient. Brain MRI showed the characteristic focal lesions appeared as xanthomas in cerebellum and occipital horns of lateral ventricles. Molecular study identified a novel homozygous frameshift mutation in CYP27A1 gene, c.1169delT (p.K391Rfs*17). Our study emphasizes the important role of early genetic testing in prevention of morbidity and mortality of the disease and proper counseling. Moreover, it shows that the absence of cataract should not rule out the diagnosis of CTX.
authors.affiliation: Medical Molecular Genetics Department, Human Genetics and Genome Research Division, National Research Centre, Giza, Cairo, Egypt.
authors.forename: Mohamed S
authors.initials: MS
authors.lastname: Abdel-Hamid
authors.affiliation: Clinical Genetics Department, Human Genetics and Genome Research Division, National Research Centre, Tahrir street, Dokki, Giza, Cairo, 12311, Egypt.
authors.forename: Mahmoud Y
authors.initials: MY
authors.lastname: Issa
authors.affiliation: Clinical Genetics Department, Human Genetics and Genome Research Division, National Research Centre, Tahrir street, Dokki, Giza, Cairo, 12311, Egypt.
authors.forename: Ghada A
authors.initials: GA
authors.lastname: Otaify
authors.affiliation: Clinical Genetics Department, Human Genetics and Genome Research Division, National Research Centre, Tahrir street, Dokki, Giza, Cairo, 12311, Egypt. dr_mahazaki@yahoo.com.
authors.forename: Maha S
authors.initials: MS
authors.lastname: Zaki
mesh_terms: D000328:Adult; D017668:Age of Onset; D001921:Brain / Q000000981:diagnostic imaging; D002386:Cataract; D002635:Chenodeoxycholic Acid / Q000627:therapeutic use; D053493:Cholestanetriol 26-Monooxygenase / Q000235:genetics*; D018450:Disease Progression; D016368:Frameshift Mutation / Q000235:genetics*; D006801:Humans; D007859:Learning Disabilities / Q000209:etiology / Q000523:psychology; D008279:Magnetic Resonance Imaging; D008297:Male; D010375:Pedigree; D011618:Psychotic Disorders / Q000188:drug therapy / Q000209:etiology / Q000523:psychology; D012640:Seizures / Q000209:etiology; D019294:Xanthomatosis, Cerebrotendinous / Q000150:complications / Q000235:genetics* / Q000523:psychology
chemical_list: D002635:Chenodeoxycholic Acid; C506831:CYP27A1 protein, human; D053493:Cholestanetriol 26-Monooxygenase
keywords: CYP27A1 gene- cerebellar manifestations; Cataract; Cerebrotendinous xanthomatosis; Cholestanol; Xanthomas