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Table of Contents    
Year : 2012  |  Volume : 60  |  Issue : 6  |  Page : 643-644

Mutation analysis of cerebrotendinous xanthomatosis in an Indian case

1 Department of Clinical Genetics, Christian Medical College, Vellore, Tamil nadu, India
2 Department of Neurology, Christian Medical College, Vellore, Tamil nadu, India
3 Department of Neurological, Neurosurgical and Behavioural Sciences, University of Siena, Siena, Italy

Date of Web Publication29-Dec-2012

Correspondence Address:
Krati Shah
Department of Clinical Genetics, Christian Medical College, Vellore, Tamil nadu
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Source of Support: None, Conflict of Interest: None

DOI: 10.4103/0028-3886.105202

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How to cite this article:
Shah K, Mathew V, Gallus GN, Dotti MT, Federico A, Danda S. Mutation analysis of cerebrotendinous xanthomatosis in an Indian case. Neurol India 2012;60:643-4

How to cite this URL:
Shah K, Mathew V, Gallus GN, Dotti MT, Federico A, Danda S. Mutation analysis of cerebrotendinous xanthomatosis in an Indian case. Neurol India [serial online] 2012 [cited 2021 Mar 6];60:643-4. Available from:


A 23-year-old Indian male visited the hospital for cognitive impairment and generalized tonic and clonic seizures. The proband was operated for bilateral cataracts at 13 years of age. He is the second child of nonconsanguineous healthy parents. The other two female siblings, 18 and 35 years of age, were asymptomatic. Seizures began at 19 years of age, and he was on antiepileptic medications. The thickening of the Achilles tendons was noticed incidentally at 16 years. Physical examination revealed bilateral enlargement of the Achilles tendon. Neurological examination revealed mild mental retardation. Magnetic resonance imaging (MRI) of brain did not reveal any abnormality. Electroencephalogram (EEG) revealed bilateral background slowing and generalized epileptiform activity. The mental age was 9 years 6 months according to BinetKamat test of Intelligence (BKT). The corresponding BKT IQ was 67 which indicates mild mental retardation. Informed consent was obtained; genomic DNA was amplified by PCR and biparallel sequencing was done using specific primers for CYP27A1. The patient was homozygous for the previously described c.526delG mutation [Figure 1] that leads to a frameshift and the introduction of a premature termination codon p.Thr175fs*5. Both the parents were heterozygous carriers for the same mutation.
Figure 1: Pathogenic mutation by Sanger sequencing

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Cerebrotendinous xanthomatosis (CTX; Online Mendelian Inheritance in Man No. 213700) was first described by van Bogaert et al. as "cholestérino segénéralisée." The deficiency of mitochondrial enzyme sterol 27-hydroxylase causes this lipid storage disorder. Sterol 27-hydroxylase has an important role in bile acid biosynthesis pathway and thus also affects cholesterol metabolism. The main clinical characteristics of CTX are infantile diarrhea, juvenile cataract, tendon xanthomas, and progressive neurological disability. Although there are case reports from Indian population, [1] but they are not about molecular diagnosis. No genetic data regarding the mutations occurring in Indian population is available. Our patient is the first molecularly characterized CTX patient from the Indian subcontinent. The homozygous mutation found in our patient was a frameshift mutation leading to stop codon, previously described in Suriname Creole patients. [2] The proband harbors from Eastern rural India and thus is likely to be of Indian origin. The frequency of carrier allele is still to be ascertained in Indian population.

There is a need to promote genetic research in Indian CTX patients. This is essential to make available genetic counseling and to improve knowledge of genetic variability in Indian population. Early diagnosis of at-risk family members using biochemical testing, or molecular genetic testing allows initiation of treatment that may prevent or limit disease manifestations as this is one of the rare genetic disorders where prevention and treatment are possible. [3] Biochemical analysis of serum cholestanol levels and bile alcohols is not easily available in India and thus molecular analysis will prove a good tool for early diagnosis.

Typical hyperintense lesions seen on T2-weighted images in the dentate nucleus and globuspallidus and other nonspecific white matter lesions are characteristic of CTX. However, our patient had no changes on MRI imaging. [4] At the time of imaging, the mean age was 37 years in the series reported by Barkhof et al. [4] It quite possible in our patient that these MRI changes may appear in the follow-up MRI. Other patients reported from India had signal alterations in cerebellar hemispheres, brainstem, and posterior cerebral white matter. [5] Our patient was referred to us with main concerns of mental retardation at 25 years of age. Juvenile cataract and tendon xanthomas gave an immediate clue to the diagnosis.

  Acknowledgment Top

We would like to thank the patient and the family for the participating in this study.

  References Top

1.Muhammed K, Nandakumar G, Saritha S. Cerebrotendinous xanthomatosis: Need for early diagnosis. Indian J Dermatol Venereol Leprol 2006;72:364-6.  Back to cited text no. 1
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2.Verrips A, Steenbergen-Spanjers GC, Luyten JA, van den Heuvel LP, Keyser A, Gabreëls FJ, et al. Two new mutations in the sterol 27-hydroxylase gene in two families lead to cerebrotendinous xanthomatosis. Hum Genet 1996;98:735-7.  Back to cited text no. 2
3.Gallus GN, Dotti MT, Federico A. Clinical and molecular diagnosis of cerebrotendinous xanthomatosis with a review of the mutations in the CYP27A1 gene. Neurol Sci 2006;27:143-9.  Back to cited text no. 3
4.Barkhof F, Verrips A, Wesseling P, van Der Knaap MS, van Engelen BG, Gabreëls FJ, et al. Cerebrotendinous xanthomatosis: The spectrum of imaging findings and the correlation with neuropathologic findings. Radiology 2000;217:869-76.  Back to cited text no. 4
5.Kamate M, Chetal V, Hattiholi V. Cerebrotendinous xanthomatosis.Indian J Pediatr 2010;77:697-8.  Back to cited text no. 5


  [Figure 1]

This article has been cited by
1 Cerebrotendinous xanthomatosis: Possibility of founder mutation in CYP27A1 gene (c.526delG) in Eastern Indian and Surinamese population
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Molecular Genetics and Metabolism Reports. 2015; 3: 33
[Pubmed] | [DOI]


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