Journal of the Formosan Medical Association
Volume 105, Issue 7 , Pages 599-603, 2006

Novel Mutation in the TSC2 Gene Associated with Prenatally Diagnosed Cardiac Rhabdomyomas and Cerebral Tuberous Sclerosis

  • Chih-Ping Chen

      Affiliations

    • Department of Obstetrics and Gynecology, Taipei, Taiwan
    • Department of Medical Research, Mackay Memorial Hospital, Taipei, Taiwan
    • Institute of Clinical Nursing, School of Nursing, National Yang-Ming University, Taipei, Taiwan
    • College of Chinese Medicine, China Medical University, Taichung, Taiwan
    • Corresponding Author InformationCorrespondence to: Dr Chih-Ping Chen, Department of Obstetrics and Gynecology, Mackay Memorial Hospital, 92, Section 2, Chung-Shan North Road, Taipei, Taiwan
    • ,
  • Yi-Ning Su

      Affiliations

    • Department of Medical Genetics, Taipei, Taiwan
    • ,
  • Chia-Cheng Hung

      Affiliations

    • Institute of Biomedical Engineering, Taipei, Taiwan
    • ,
  • Jin-Chung Shih

      Affiliations

    • Department of Obstetrics and Gynecology, National Taiwan University Hospital, Taipei, Taiwan
    • ,
  • Wayseen Wang

      Affiliations

    • Department of Medical Research, Mackay Memorial Hospital, Taipei, Taiwan

Received 18 April 2005; received in revised form 27 May 2005; accepted 13 September 2005.

Article Outline

Cardiac rhabdomyomas are prenatal echocardiographic markers for tuberous sclerosis complex (TSC). TSC is caused by mutations in the genes TSC1 and TSC2. We report a 28-year-old, gravida 5, para 2, woman with an uncomplicated pregnancy until prenatal ultrasound at 34 weeks' gestation revealed fetal cardiac tumors. Ultrafast magnetic resonance imaging (MRI) at 36 weeks' gestation showed cardiac rhab-domyomas and small subependymal tubers. At 39 weeks' gestation, a 2262 g female infant was delivered uneventfully. Postnatal echocardiography confirmed cardiac rhabdomyomas and MRI verified small cerebral subependymal tubers. Mutational analysis of TSC1 and TSC2 genes using denaturing high-performance liquid chromatography and direct sequencing of the genes was performed and revealed that the parents had wildtype DNA, while the proband was heterozygous for a novel de novo nonsense mutation, c.4830 G > A, in exon 36 of the TSC2 gene, resulting in a change of codon 1610 TGG (tryptophan) to TGA (stop codon). The mutation predicted a W1610X premature termination of the tuberin protein. These findings support an association between a TSC2 de novo nonsense mutation and prenatally detected cardiac rhabdomyomas and cerebral tuberous sclerosis. Familial molecular analysis of TSC1 and TSC2 in cases with prenatally diagnosed cardiac rhabdomyomas and cerebral tuberous sclerosis lesions is helpful in prenatal diagnosis and genetic counseling.

Key Words:  cardiac rhabdomyoma , cerebral tuberous sclerosis , HPLC , tuberlin , tuberous sclerosis complex

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PII: S0929-6646(09)60157-1

doi:10.1016/S0929-6646(09)60157-1

Journal of the Formosan Medical Association
Volume 105, Issue 7 , Pages 599-603, 2006

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