PMC3417334_01
(a) Craniometaphyseal dysplasia (CMD) patient 1 presents with frontal bossing, macrocephaly, and a left facial palsy. Her distal femur and proximal tibia show typical metaphyseal flaring. (b) CMD patient 2 presents with characteristic facies, hyperostotic cranial bones, and flaring of long bone metaphyses. (c) Electropherogram showing a heterozygous deletion in exon 7 of the ANKH genomic DNA from CMD patient 1. (d) Sequence comparison to wild type sequence shows an 18 bp/6 aa in-frame deletion. (e) Electropherogram showing a deletion in exon 10 of the ANKH genomic DNA from CMD patient 2. (f) Sequence comparison to wild type sequence shows a 12 bp/4 aa in-frame deletion. (g) Mutations for CMD located in exons 7, 8, 9, and 10 of ANKH. New mutations indicated in red.
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F1
Patient 2 (Fig. 1b) is a 5-year-old female who was evaluated for thickened calvarium and temporal bone with bony sclerosis of the internal auditory canals, cochleas, and semicircular canals, bilateral obliteration of mastoid air cells, and mixed bilateral hearing loss. Sequence analysis of ANKH in patient 1 detected an extensive in-frame deletion of 18 nucleotides in exon 7 (c853-870del) affecting amino acids 285 to 290 (pV285-Y290del) (Gen- Bank #BC014526) (Fig. 1c,d). Patient 2 had an extensive 12-base pair in-frame mutation in exon 10 of ANKH (c1178-1189del) affecting amino acids 393 to 396 (pT393-K396del) (Fig. 1e,f).