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Journal of Inherited Metabolic Disease

, Volume 31, Supplement 2, pp 317–322 | Cite as

Congenital generalized lipodystrophy in an Indian patient with a novel mutation in BSCL2 gene

  • H. U. Shirwalkar
  • Z. M. Patel
  • J. Magre
  • P. Hilbert
  • L. Van Maldergem
  • R. R. Mukhopadhyay
  • A. Maitra
Short Report

Summary

Congenital generalized lipodystrophy (CGL) is an autosomal recessive metabolic syndrome with involvement of multiple organs. Mutations in BSCL2 are known to be associated with a severe form of CGL and mental retardation (MR). The genetic heterogeneity in CGL patients is accompanied by phenotypic heterogeneity in different ethnic groups. Studies in the Indian context are very few in this regard. We report here a detailed clinical analysis of a CGL case from infancy to adult hood. Interestingly, the patient was found to be homozygous for a novel BSCL2 mutation, but with normal intellectual development contrasting with the MR associated with BSCL2 mutation in CGL patients. The biochemical investigations at the time of diagnosis (9 months) included total cholesterol, total lipids, triglycerides, phospholipids, β-lipoprotein and free fatty acids, which were above normal limits. The clinical phenotype, viz. lack of subcutaneous fat, hepatosplenomegaly, cardiomegaly, and advanced bone age was also documented. The patient was found to be insulin resistant and diabetes mellitus was diagnosed by age 13 years. Ultrasonography of the ovaries at age 22 showed polycystic features with elevated levels of gonadotropins and negligible levels of serum leptin. For genetic analysis, direct DNA sequencing of BSCL2 was carried out and disclosed an 11-base-pair deletion in exon 6 (H217fsX272) resulting in a truncated protein. This is a novel mutation that contributes to CGL formation in a family of Indian origin and adds to the array of variants reported in this disorder. Moreover, the novel mutation is found to be associated with normal intellectual ability.

Keywords

Mental Retardation Polycystic Ovary Polycystic Ovary Syndrome Acanthosis Nigricans Bone Marrow Region 
These keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.

Abbreviations

AGPAT

1-acylglycerol-3-phosphate O-acyltransferase 2

BSCL

Berardinelli–Seip congenital lipodystrophy 2

CGL

congenital generalized lipodystrophy

FSH

follicle-stimulating hormone

LDL

low-density lipoprotein

LH

leutinizing hormone

Notes

Acknowledgement

The authors wish to thank Dr C. P. Puri, Director, NIRRH for his support in carrying out this study. We thank Ms Madhavi Pusalkar for helping in carrying out the biochemical estimations .We also wish to thank the Lady Tata Memorial Trust and Indian Council of Medical Research for providing financial support to H.S. for this work.

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Copyright information

© Springer Science+Business Media B.V. 2008

Authors and Affiliations

  • H. U. Shirwalkar
    • 1
  • Z. M. Patel
    • 2
  • J. Magre
    • 3
  • P. Hilbert
    • 4
  • L. Van Maldergem
    • 5
  • R. R. Mukhopadhyay
    • 6
  • A. Maitra
    • 1
  1. 1.Department of Molecular EndocrinologyNational Institute for Research in Reproductive Health (ICMR)ParelIndia
  2. 2.Genetic Research CentreNational Institute for Research in Reproductive HealthParelIndia
  3. 3.INSERM U 402, Faculty of MedicineSt. AntonieFrance
  4. 4.Molecular Genetics DepartmentInstitute de Pathologie et de GénétiqueGerpinnesBelgium
  5. 5.Centre de Génétique HumaineUniversité de LiègeLiègeBelgium
  6. 6.Molecular Biology and Agriculture Development LaboratoryBhabha Atomic Research CentreTrombayIndia

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