TY - JOUR
T1 - A gene for congenital generalized lipodystrophy maps to human chromosome 9q34
AU - Garg, Abhimanyu
AU - Wilson, Ross
AU - Barnes, Robert
AU - Arioglu, Elif
AU - Zaidi, Zohra
AU - Gurakan, Figen
AU - Kocak, Nurten
AU - O'Rahilly, Stephen
AU - Taylor, Simeon I.
AU - Patel, Shailendra B.
AU - Bowcock, Anne M.
PY - 1999
Y1 - 1999
N2 - Congenital generalized lipodystrophy (CGL, Berardinelli-Seip Syndrome, OMIM 269700) is a rare autosomal recessive disorder characterized by near complete absence of adipose tissue from birth. Affected individuals have marked insulin resistance, hypertriglyceridemia and acanthosis nigricans, and develop diabetes mellitus during teenage years. The genetic defect for CGL is unknown. A semi-automated genome-wide scan with a set of highly polymorphic short tandem repeats (STR) was carried out in 17 well-characterized pedigrees and identified a locus for CGL to chromosome 9q34. The maximum two-point lod score obtained was 3.6 at D9S1818 (θ(max) = 0.05). There was evidence for genetic heterogeneity (α = 0.73) and 2 of the pedigrees were unlinked. Multipoint linkage analysis excluding the 2 unlinked families yielded a peak lod score of 5.4 between loci D9S1818 and D9S1826. The CGL 1 critical region harbors a plausible candidate gene encoding the retinoid X receptor α (RXRA) that plays a central role in adipocyte differentiation. Identification of the CGL gene(s) will contribute to our understanding of the adipocyte differentiation and elucidation of the mechanisms of insulin resistance in disorders of adipose tissue.
AB - Congenital generalized lipodystrophy (CGL, Berardinelli-Seip Syndrome, OMIM 269700) is a rare autosomal recessive disorder characterized by near complete absence of adipose tissue from birth. Affected individuals have marked insulin resistance, hypertriglyceridemia and acanthosis nigricans, and develop diabetes mellitus during teenage years. The genetic defect for CGL is unknown. A semi-automated genome-wide scan with a set of highly polymorphic short tandem repeats (STR) was carried out in 17 well-characterized pedigrees and identified a locus for CGL to chromosome 9q34. The maximum two-point lod score obtained was 3.6 at D9S1818 (θ(max) = 0.05). There was evidence for genetic heterogeneity (α = 0.73) and 2 of the pedigrees were unlinked. Multipoint linkage analysis excluding the 2 unlinked families yielded a peak lod score of 5.4 between loci D9S1818 and D9S1826. The CGL 1 critical region harbors a plausible candidate gene encoding the retinoid X receptor α (RXRA) that plays a central role in adipocyte differentiation. Identification of the CGL gene(s) will contribute to our understanding of the adipocyte differentiation and elucidation of the mechanisms of insulin resistance in disorders of adipose tissue.
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U2 - 10.1210/jcem.84.9.6103
DO - 10.1210/jcem.84.9.6103
M3 - Article
C2 - 10487716
AN - SCOPUS:0033305362
SN - 0021-972X
VL - 84
SP - 3390
EP - 3394
JO - Journal of Clinical Endocrinology and Metabolism
JF - Journal of Clinical Endocrinology and Metabolism
IS - 9
ER -