Identification of a Frameshift Mutation in Osterix in a Patient with Recessive Osteogenesis Imperfecta Pablo Lapunzina, Mona Aglan, Samia Temtamy, José.

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Identification of a Frameshift Mutation in Osterix in a Patient with Recessive Osteogenesis Imperfecta Pablo Lapunzina, Mona Aglan, Samia Temtamy, José A. Caparrós-Martín, Maria Valencia, Rocío Letón, Victor Martínez-Glez, Rasha Elhossini, Khalda Amr, Nuria Vilaboa, Victor L. Ruiz-Perez The American Journal of Human Genetics Volume 87, Issue 1, Pages 110-114 (July 2010) DOI: 10.1016/j.ajhg.2010.05.016 Copyright © 2010 The American Society of Human Genetics Terms and Conditions

Figure 1 Clinical Findings in the Patient with an OSX Mutation (A) Photographs of the reported patient showing bowing of the long bones of the arms (top) and sabre tibia (bottom). (B–E) Radiographical findings in the proband at the age of 8 years. (B) X-ray of the right upper limb (lateral view) demonstrating anterior bowing, deformed irregular humerus, radius, and ulna, and generalized decreased bone density. An old, improperly healed fracture at the lower third of the humerus and transverse fractures of the radius and ulna are indicated by small arrows. The long arrow designates a transverse line of arrested bone growth at the lower end of the radius. (C) X-ray of the right leg (lateral view) showing decreased bone density with anterior bowing of the tibia and fibula and transverse fracture at the lower third of the tibia (arrow). (D) X-ray of the pelvis and upper ends of femora (anterior-posterior view) demonstrating a deformed asymmetric pelvis with thin laterally displaced neck of the femur, bilaterally, mostly on the right side. There is an old, improperly healed fracture at the upper end of right femur with callus formation (arrow). (E) X-ray of the skull (lateral view) showing wormian bones at the occipital region (arrow). The American Journal of Human Genetics 2010 87, 110-114DOI: (10.1016/j.ajhg.2010.05.016) Copyright © 2010 The American Society of Human Genetics Terms and Conditions

Figure 2 Identification of a Frameshift Mutation in Osterix (A) Pedigree of the OI family analyzed in this study; the proband (P) is designated with an arrow. (B) Alignment of genomic sequence chromatograms corresponding to an area encompassing the c.1052delA mutation from a normal individual (N), a heterozygous carrier (C), and the proband (P). The adenine deleted in the patient is squared in gray. Numbering of the mutation correlates to the reference sequence NM_152860.1, taking the A of the translation start site as nucleotide + 1. (C) Protein effect of the c.1052delA mutation. The picture on the top shows the position of the three zinc fingers represented by blue rectangles in the normal (Wt) and mutant (Mut) SP7 proteins. The mutant protein is missing the third zinc finger, and the new residues incorporated after the frameshift are indicated in red. The lower panel shows the sequence of amino acids corresponding to the DNA binding region of normal and mutant OSX. Conserved cysteine and histidine residues involved in zinc ion coordination corresponding to each individual zinc finger are highlighted in different colors. The amino acids inserted after the mutation are in red. Protein numbering is related to the reference sequence NP_690599.1. The American Journal of Human Genetics 2010 87, 110-114DOI: (10.1016/j.ajhg.2010.05.016) Copyright © 2010 The American Society of Human Genetics Terms and Conditions