Autosomal dominant pseudohypoparathyroidism type Ib is associated with a heterozygous microdeletion that likely disrupts a putative imprinting control element of GNAS
J. Clin. Invest. Murat Bastepe, et al. 112:1255 doi:10.1172/JCI19159 [Go to this article.]

Figure 3
Identification of the 3-kb microdeletion in kindred F. (a) Genomic structure of the region surrounding the microdeletion. Filled boxes and connecting lines depict STX16 exons and introns, respectively. Horizontal bars represent the probes used in Southern blot analysis. Arrowheads indicate the location of the two 391-bp direct repeats (nucleotides 3,786–4,176 and nucleotides 6,764–7,154 of AL139349). Arrows indicate the approximate positions of the PCR primers used for amplification of the wild-type and mutant alleles. (b) Southern blot analysis of genomic DNA from selected members of kindred F (22). Affected individuals, filled symbols and b identification numbers. Healthy individuals, open symbols and plain numbers. Unaffected obligate gene carrier, gray circles and b i numbers. Genomic DNA digested with either AvrII (top) or ClaI (bottom) was separated on 0.8% agarose and transferred onto nitrocellulose before hybridization with the radiolabeled probe. (c) PCR amplification of the wild-type (∼4.3 kb) and mutant (∼1.3 kb) alleles from genomic DNA of members of kindred F (22). Nucleotide sequence analysis of the 1.3-kb PCR product derived from the mutant allele revealed that 2,978 bp were deleted (based on AL139349 sequence), although this number varies due to polymorphisms including the dinucleotide repeat polymorphism 261P9-CA1 (see Supplemental Table 1; www.jci.org/cgi/content/full/112/8/1255/DC1).