Phenotypic and Genetic Heterogeneity in Congenital Generalized Lipodystrophy

Anil K. Agarwal, Vinaya Simha, Elif Arioglu Oral, Stephanie A. Moran, Phillip Gorden, Stephen O'Rahilly, Zohra Zaidi, Figen Gurakan, Silva A. Arslanian, Aharon Klar, Alyne Ricker, Neil H. White, Lutz Bindl, Karen Herbst, Kurt Kennel, Shailesh B. Patel, Lihadh Al-Gazali, Abhimanyu Garg

Research output: Contribution to journalArticle

161 Citations (Scopus)

Abstract

Congenital generalized lipodystrophy (CGL) is a rare autosomal recessive disorder characterized by near complete absence of adipose tissue from birth. Recently, mutations in 1-acylglycerol-3-phosphate O-acyltransferase 2 (AGPAT2) and Berardinelli-Seip congenital lipodystrophy 2 (BSCL2) genes were reported in pedigrees linked to chromosomes 9q34 and 11q13, respectively. There are limited data regarding phenotypic differences between the various subtypes of CGL. Furthermore, whether there are additional loci for CGL remains unknown. Therefore, we genotyped 45 pedigrees with CGL for AGPAT2 and BSCL2 loci and compared the phenotypes in the various subtypes. Twenty-six pedigrees harbored mutations, including seven novel variants, in the AGPAT2 gene, and 11 pedigrees harbored mutations in the BSCL2 gene, including five novel variants. Eight pedigrees had no substantial alterations in either gene. Of these, three informative pedigrees showed no linkage to markers spanning the AGPAT2 and BSCL2 loci, and in six of the affected subjects, the transcripts of AGPAT2 and BSCL2 were normal. All subtypes of CGL showed high prevalence of diabetes, hypertriglyceridemia, and acanthosis nigricans. However, patients with BSCL2 mutations had lower serum leptin levels, an earlier onset of diabetes, and higher prevalence of mild mental retardation compared with other subtypes. We conclude that besides AGPAT2 and BSCL2, there may be additional loci for CGL. The genetic heterogeneity in CGL patients is accompanied by phenotypic heterogeneity.

Original languageEnglish (US)
Pages (from-to)4840-4847
Number of pages8
JournalJournal of Clinical Endocrinology and Metabolism
Volume88
Issue number10
DOIs
StatePublished - Oct 2003

Fingerprint

Congenital Generalized Lipodystrophy
Glycerides
Acyltransferases
Genetic Heterogeneity
Phosphates
Genes
Pedigree
Medical problems
1-Acylglycerol-3-Phosphate O-Acyltransferase
Chromosomes
Leptin
Mutation
Tissue
Acanthosis Nigricans
Hypertriglyceridemia

ASJC Scopus subject areas

  • Biochemistry
  • Endocrinology, Diabetes and Metabolism

Cite this

Phenotypic and Genetic Heterogeneity in Congenital Generalized Lipodystrophy. / Agarwal, Anil K.; Simha, Vinaya; Oral, Elif Arioglu; Moran, Stephanie A.; Gorden, Phillip; O'Rahilly, Stephen; Zaidi, Zohra; Gurakan, Figen; Arslanian, Silva A.; Klar, Aharon; Ricker, Alyne; White, Neil H.; Bindl, Lutz; Herbst, Karen; Kennel, Kurt; Patel, Shailesh B.; Al-Gazali, Lihadh; Garg, Abhimanyu.

In: Journal of Clinical Endocrinology and Metabolism, Vol. 88, No. 10, 10.2003, p. 4840-4847.

Research output: Contribution to journalArticle

Agarwal, AK, Simha, V, Oral, EA, Moran, SA, Gorden, P, O'Rahilly, S, Zaidi, Z, Gurakan, F, Arslanian, SA, Klar, A, Ricker, A, White, NH, Bindl, L, Herbst, K, Kennel, K, Patel, SB, Al-Gazali, L & Garg, A 2003, 'Phenotypic and Genetic Heterogeneity in Congenital Generalized Lipodystrophy', Journal of Clinical Endocrinology and Metabolism, vol. 88, no. 10, pp. 4840-4847. https://doi.org/10.1210/jc.2003-030855
Agarwal, Anil K. ; Simha, Vinaya ; Oral, Elif Arioglu ; Moran, Stephanie A. ; Gorden, Phillip ; O'Rahilly, Stephen ; Zaidi, Zohra ; Gurakan, Figen ; Arslanian, Silva A. ; Klar, Aharon ; Ricker, Alyne ; White, Neil H. ; Bindl, Lutz ; Herbst, Karen ; Kennel, Kurt ; Patel, Shailesh B. ; Al-Gazali, Lihadh ; Garg, Abhimanyu. / Phenotypic and Genetic Heterogeneity in Congenital Generalized Lipodystrophy. In: Journal of Clinical Endocrinology and Metabolism. 2003 ; Vol. 88, No. 10. pp. 4840-4847.
@article{9e7d3ceee5714c80b31f4c53e5c39cc2,
title = "Phenotypic and Genetic Heterogeneity in Congenital Generalized Lipodystrophy",
abstract = "Congenital generalized lipodystrophy (CGL) is a rare autosomal recessive disorder characterized by near complete absence of adipose tissue from birth. Recently, mutations in 1-acylglycerol-3-phosphate O-acyltransferase 2 (AGPAT2) and Berardinelli-Seip congenital lipodystrophy 2 (BSCL2) genes were reported in pedigrees linked to chromosomes 9q34 and 11q13, respectively. There are limited data regarding phenotypic differences between the various subtypes of CGL. Furthermore, whether there are additional loci for CGL remains unknown. Therefore, we genotyped 45 pedigrees with CGL for AGPAT2 and BSCL2 loci and compared the phenotypes in the various subtypes. Twenty-six pedigrees harbored mutations, including seven novel variants, in the AGPAT2 gene, and 11 pedigrees harbored mutations in the BSCL2 gene, including five novel variants. Eight pedigrees had no substantial alterations in either gene. Of these, three informative pedigrees showed no linkage to markers spanning the AGPAT2 and BSCL2 loci, and in six of the affected subjects, the transcripts of AGPAT2 and BSCL2 were normal. All subtypes of CGL showed high prevalence of diabetes, hypertriglyceridemia, and acanthosis nigricans. However, patients with BSCL2 mutations had lower serum leptin levels, an earlier onset of diabetes, and higher prevalence of mild mental retardation compared with other subtypes. We conclude that besides AGPAT2 and BSCL2, there may be additional loci for CGL. The genetic heterogeneity in CGL patients is accompanied by phenotypic heterogeneity.",
author = "Agarwal, {Anil K.} and Vinaya Simha and Oral, {Elif Arioglu} and Moran, {Stephanie A.} and Phillip Gorden and Stephen O'Rahilly and Zohra Zaidi and Figen Gurakan and Arslanian, {Silva A.} and Aharon Klar and Alyne Ricker and White, {Neil H.} and Lutz Bindl and Karen Herbst and Kurt Kennel and Patel, {Shailesh B.} and Lihadh Al-Gazali and Abhimanyu Garg",
year = "2003",
month = "10",
doi = "10.1210/jc.2003-030855",
language = "English (US)",
volume = "88",
pages = "4840--4847",
journal = "Journal of Clinical Endocrinology and Metabolism",
issn = "0021-972X",
publisher = "The Endocrine Society",
number = "10",

}

TY - JOUR

T1 - Phenotypic and Genetic Heterogeneity in Congenital Generalized Lipodystrophy

AU - Agarwal, Anil K.

AU - Simha, Vinaya

AU - Oral, Elif Arioglu

AU - Moran, Stephanie A.

AU - Gorden, Phillip

AU - O'Rahilly, Stephen

AU - Zaidi, Zohra

AU - Gurakan, Figen

AU - Arslanian, Silva A.

AU - Klar, Aharon

AU - Ricker, Alyne

AU - White, Neil H.

AU - Bindl, Lutz

AU - Herbst, Karen

AU - Kennel, Kurt

AU - Patel, Shailesh B.

AU - Al-Gazali, Lihadh

AU - Garg, Abhimanyu

PY - 2003/10

Y1 - 2003/10

N2 - Congenital generalized lipodystrophy (CGL) is a rare autosomal recessive disorder characterized by near complete absence of adipose tissue from birth. Recently, mutations in 1-acylglycerol-3-phosphate O-acyltransferase 2 (AGPAT2) and Berardinelli-Seip congenital lipodystrophy 2 (BSCL2) genes were reported in pedigrees linked to chromosomes 9q34 and 11q13, respectively. There are limited data regarding phenotypic differences between the various subtypes of CGL. Furthermore, whether there are additional loci for CGL remains unknown. Therefore, we genotyped 45 pedigrees with CGL for AGPAT2 and BSCL2 loci and compared the phenotypes in the various subtypes. Twenty-six pedigrees harbored mutations, including seven novel variants, in the AGPAT2 gene, and 11 pedigrees harbored mutations in the BSCL2 gene, including five novel variants. Eight pedigrees had no substantial alterations in either gene. Of these, three informative pedigrees showed no linkage to markers spanning the AGPAT2 and BSCL2 loci, and in six of the affected subjects, the transcripts of AGPAT2 and BSCL2 were normal. All subtypes of CGL showed high prevalence of diabetes, hypertriglyceridemia, and acanthosis nigricans. However, patients with BSCL2 mutations had lower serum leptin levels, an earlier onset of diabetes, and higher prevalence of mild mental retardation compared with other subtypes. We conclude that besides AGPAT2 and BSCL2, there may be additional loci for CGL. The genetic heterogeneity in CGL patients is accompanied by phenotypic heterogeneity.

AB - Congenital generalized lipodystrophy (CGL) is a rare autosomal recessive disorder characterized by near complete absence of adipose tissue from birth. Recently, mutations in 1-acylglycerol-3-phosphate O-acyltransferase 2 (AGPAT2) and Berardinelli-Seip congenital lipodystrophy 2 (BSCL2) genes were reported in pedigrees linked to chromosomes 9q34 and 11q13, respectively. There are limited data regarding phenotypic differences between the various subtypes of CGL. Furthermore, whether there are additional loci for CGL remains unknown. Therefore, we genotyped 45 pedigrees with CGL for AGPAT2 and BSCL2 loci and compared the phenotypes in the various subtypes. Twenty-six pedigrees harbored mutations, including seven novel variants, in the AGPAT2 gene, and 11 pedigrees harbored mutations in the BSCL2 gene, including five novel variants. Eight pedigrees had no substantial alterations in either gene. Of these, three informative pedigrees showed no linkage to markers spanning the AGPAT2 and BSCL2 loci, and in six of the affected subjects, the transcripts of AGPAT2 and BSCL2 were normal. All subtypes of CGL showed high prevalence of diabetes, hypertriglyceridemia, and acanthosis nigricans. However, patients with BSCL2 mutations had lower serum leptin levels, an earlier onset of diabetes, and higher prevalence of mild mental retardation compared with other subtypes. We conclude that besides AGPAT2 and BSCL2, there may be additional loci for CGL. The genetic heterogeneity in CGL patients is accompanied by phenotypic heterogeneity.

UR - http://www.scopus.com/inward/record.url?scp=10744220431&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=10744220431&partnerID=8YFLogxK

U2 - 10.1210/jc.2003-030855

DO - 10.1210/jc.2003-030855

M3 - Article

C2 - 14557463

AN - SCOPUS:10744220431

VL - 88

SP - 4840

EP - 4847

JO - Journal of Clinical Endocrinology and Metabolism

JF - Journal of Clinical Endocrinology and Metabolism

SN - 0021-972X

IS - 10

ER -