Spondyloepimetaphyseal dysplasia with joint laxity (SEMDJL), leptodactylic (lepto-SEMDJL) or Hall type, is an autosomal-dominant skeletal dysplasia manifesting with short stature, joint laxity with dislocation(s), limb malalignment, and spinal deformity. Its causative gene mutation has not yet been discovered. We captured and sequenced the exomes of eight affected individuals in six unrelated kindreds (three individuals in a family and five simplex individuals). Five novel sequence variants in KIF22, which encodes a member of the kinesin-like protein family, were identified in seven individuals. Sanger sequencing of KIF22 confirmed that c.443C>T (p.Pro148Ser) cosegregated with the phenotype in the affected individuals in the family; c.442C>T (p.Pro148Leu) or c.446G>A (p.Arg149Gln) was present in four of five simplex individuals, but was absent in unaffected individuals in their family and 505 normal cohorts. KIF22 mRNA was detected in human bone, cartilage, joint capsule, ligament, skin, and primary cultured chondrocytes. In silico analysis of KIF22 protein structure indicates that Pro148 and Arg149 are important in maintaining hydrogen bonds in the ATP binding and motor domains of KIF22. We conclude that these mutations in KIF22 cause lepto-SEMDJL.
A high-spin isomer in 145 Sm was discovered by using Inverse kinematic reactions, 20 Ne e Xe,a7n) 145 Sm and 16 0 e 36 Xe,7n) 145 Sm. The half life was determined to be 0.96 J.LSec. Sixty-five 1-rays were identified by the /')'-coincidence measurements to belong to the isomer decay. The low-lying level scheme of 145 Sm was established in detail by the in-beam 1-ray measurements using the 139 La e 0 B,4n) 145 Sm reaction. A complex decay scheme of this isomer was constructed by using the data obtained from the 136 Xe induced reactions, combining the informations of low-lying states mentioned above. The excitation energy of this isomer was determined to be 8.8 MeV. The /')'-coincidence measurement using the 138 Ba (13 C,6n) 145 Sm reaction was also performed. Based on this information, the level scheme above the high-spin isomer was extended up to the state at 14.6 MeV. A 1-ray angular distribution measurement using the same reaction with pulsed beam was carried out and was used to assign a spin value of each level. Low-lying states in 145 Sm were interpreted to originate from a single neutron coupled to the 144 Sm core excitation. Experimental yrast states were compared with a calculation of a deformed independent particle model (DIPM). A configuration of the high-spin isomer was deduced by the DIPM calculation to be { 7r h ll /2 2 v (f 7 /2 h 9/2 i 13/2) } 49/2+ .
It is debatable whether Hajdu-Cheney syndrome (HCS) and serpentine fibula-polycystic kidney syndrome (SFPKS) represent a single clinical entity with a variable degree of expression or two different entities, because both disorders share common clinical and radiological manifestations, including similar craniofacial characteristics, and defective bone mineralization. Since it was shown that heterozygous truncating mutations in NOTCH2 are responsible for both HCS and SFPKS, 37 patients with HCS and four patients with SFPKS are reported. To elucidate the clinical consequences of NOTCH2 mutations, we present detailed clinical information for seven patients with truncating mutations in exon 34 of NOTCH2, six with HCS and one with SFPKS. In addition, we review all the reported patients whose clinical manifestations are available. We found 13 manifestations including craniofacial features, acroosteolysis, Wormian bones, and osteoporosis in >75% of NOTCH2-positive patients. Acroosteolysis was observed in two patients with SFPKS and bowing fibulae were found in two patients with HCS. These clinical and molecular data would support the notion that HCS and SFPKS are a single disorder.
Our data suggest that different POU3F4 mutations might show different recurrence rate in siblings of the IP type III families, especially in East Asian population. Genetic counseling should be provided accordingly.
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