title: Congenital generalized lipodystrophy in an Indian patient with a novel mutation in BSCL2 gene.
abstract: 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.
authors.affiliation: Department of Molecular Endocrinology, National Institute for Research in Reproductive Health (ICMR), Jehangir Merwanji Street, Parel, Mumbai, 400 012, India.
authors.forename: H U
authors.initials: HU
authors.lastname: Shirwalkar
authors.forename: Z M
authors.initials: ZM
authors.lastname: Patel
authors.forename: J
authors.initials: J
authors.lastname: Magre
authors.forename: P
authors.initials: P
authors.lastname: Hilbert
authors.forename: L
authors.initials: L
authors.lastname: Van Maldergem
authors.forename: R R
authors.initials: RR
authors.lastname: Mukhopadhyay
authors.forename: A
authors.initials: A
authors.lastname: Maitra
mesh_terms: D000293:Adolescent; D000328:Adult; D002648:Child; D002657:Child Development; D002675:Child, Preschool; D004252:DNA Mutational Analysis; D018450:Disease Progression; D005091:Exons; D017809:Fatal Outcome; D005260:Female; D044388:GTP-Binding Protein gamma Subunits / Q000235:genetics*; D020022:Genetic Predisposition to Disease; D006720:Homozygote; D006801:Humans; D007194:India; D007223:Infant; D007360:Intelligence; D052497:Lipodystrophy, Congenital Generalized / Q000150:complications / Q000175:diagnosis / Q000235:genetics* / Q000523:psychology; D010641:Phenotype; D051437:Renal Insufficiency / Q000209:etiology; D017384:Sequence Deletion; D055815:Young Adult
chemical_list: C432679:BSCL2 protein, human; D044388:GTP-Binding Protein gamma Subunits