Fig. 1.

BSCL2 mutations in a family with congenital lipodystrophy. (A) Family tree of male patient 1 (P1) and five family members. P1 and his sister [patient 2 (P2)] exhibited lipoatrophy; his mother, stepfather, and stepsister were not affected. P1 and P2 were compound heterozygotes for a G to T mutation in exon 5 (green) and a 19-nt deletion in exon 2 (red) of the BSCL2 gene. The mother was heterozygous for this 19-nt deletion. (B) Detection of mutations by sequence analysis of the BSCL2 gene. A heterozygous 19-bp deletion from nucleotides 358 to 376 in exon 2 in both the subject and her brother causes a frameshift (S119fsX155). The G to T mutation in exon 5 converts codon 253 (glutamic acid) to a stop codon (E253X), resulting in premature termination. Ctl, control sample from an unrelated healthy man; M, mother. Arrowheads indicate the first base of the respective mutation. (C and D) The proportion of mutant to normal sequence in patient samples indicates heterozygosity for each mutation. PCR fragments amplified from patient DNA were subcloned followed by sequencing of plasmids isolated in randomly picked colonies. (E) Physical appearance of P1 with marked absence of s.c. fat and muscular appearance.