Figure 1

Pedigree, FISH and X chromosome inactivation of patient 1 and three healthy female relatives. A. Pedigree of patient’s 1 family. Patient 1 (III-1) is affected by MLS syndrome, while her mother (II-1), her maternal aunt (II-2) and her maternal grandmother (I-1) are asymptomatic. FISH analysis with BAC RP11-163I1, spanning the HCCS gene on metaphase spreads of the four females revealed one signal in patient 1 (III-1), her mother (II-1) and her aunt (II-2). For the maternal grandmother (I-1), two signals for RP11-163I1 and three signals for the X centromere probe DXZ1 were obtained. BAC RP11-163I1 and DXZ1 were labelled with Spectrum Green-dUTP. Arrows point to the wild-type X chromosome (WT X) and the X chromosome with the microdeletion at Xp22.2 (del(X)). X chromosome inactivation was determined by analysing the methylation status of the androgen receptor gene at Xq12. Predigestion of genomic DNA isolated from lymphocytes with and without Hpa II is indicated by (+) and (-), respectively. Representative electropherograms show the different AR alleles (designated as 1, 2, 3 and 4) in the four females. Females II-1, II-2 and III-1 have extremely skewed X inactivation (upper electropherograms indicated with +). B. Physical map of part of the Xp22.3 and Xp22.2 regions that are indicated by horizontal grey bars; Mbs and the telomere (tel) to centromere (cen) orientation are given. Arrows represent selected genes in Xp22 and gene symbols are given; arrowheads indicate the 5′ → 3′ transcription direction of the genes. BAC RP11-163I1 (RP11 Human BAC Library) and four Xp22.2 fosmid (WIBR-2 Human Fosmid Library) clones are indicated by black bars and names are given. Interstitial deletions found in patients 1 (P1) and 6 (P6) are depicted as horizontal black lines and the size of each deletion is given. Dotted and wavy lines indicate that the deletion breakpoints were not fine-mapped.