Soraya Beiraghi

WNT5A mutations in patients with autosomal dominant Robinow syndrome.

Robinow syndrome is a skeletal dysplasia with both autosomal dominant and autosomal recessive inheritance patterns. It is characterized by short stature, limb shortening, genital hypoplasia, and craniofacial abnormalities. The etiology of dominant Robinow syndrome is unknown; however, the phenotypically more severe autosomal recessive form of Robinow syndrome has been associated with mutations in the orphan tyrosine kinase receptor, ROR2, which has recently been identified as a putative WNT5A receptor. Here, we show that two different missense mutations in WNT5A, which result in amino acid substitutions of highly conserved cysteines, are associated with autosomal dominant Robinow syndrome. One mutation has been found in all living affected members of the original family described by Meinhard Robinow and another in a second unrelated patient. These missense mutations result in decreased WNT5A activity in functional assays of zebrafish and Xenopus development. This work suggests that a WNT5A/ROR2 signal transduction pathway is important in human craniofacial and skeletal development and that proper formation and growth of these structures is sensitive to variations in WNT5A function. Developmental Dynamics 239:327–337, 2010.

The effects of a companion animal on distress in children undergoing dental procedures.

The purpose of our pilot study was to evaluate the effects of a companion animal (dog) on physiologic arousal and behavioral distress among children undergoing a dental procedure. A repeated measures experimental design was used to study 40 children between the ages of 7 and 11 years who were undergoing procedures in a pediatric dental clinic. Half the children had the dog present during the procedure and half did not. Data were obtained before, during, and after the procedure. Behavioral distress was measured using the Observational Scale of Behavioral Distress; procedures were videotaped. Physiologic arousal was measured using a YSI telethermometer taped to the childs index finger. Students t-test and repeated measures analysis of variance were used to answer the research question. No significant differences in behavioral distress or physiologic arousal were found between experimental and control groups. Further analysis revealed that for children who initially verbalized distress on arrival at the clinic, the presence of the dog decreased physiologic arousal during the time the child was on the dental table waiting for the dentist to arrive. Further research should be conducted to verify the effect of a companion animal on initial stress experienced by children for whom the visit to the dentist is most stressful.

Identification and characterization of a novel gene disrupted by a pericentric inversion inv(4)(p13.1q21.1) in a family with cleft lip.

Cleft lip with or without cleft palate is a common birth defect affecting 1 in every 700 live births. Several genetic loci are believed to be involved in the pathogenesis of syndromic and non-syndromic clefting. We identified a pericentric inversion of chromosome 4, inv(4)(p13q21) that segregates with cleft lip in a two-generation family. By using a combination of fluorescence in situ hybridization, yeast artificial chromosome, bacterial artificial chromosome contig mapping, and database searching we mapped and sequenced the inversion breakpoint region. The pericentric inversion disrupts a gene (ACOD4) on chromosome 4q21 that codes for a novel acyl-CoA desaturase enzyme. The 3.0 kb human ACOD4 cDNA spans approximately 170 kb and is composed of five exons of ACOD4. The inversion breakpoint is located in the second exon. The 3.0 kb mRNA is expressed at high level in fetal brain; a lower expression level was found in fetal kidney. No expression of ACOD4 was detected in fetal lung or liver or in adult tissues. The five exons code for a protein of 330 amino acids, with a predicted molecular weight of 37.5 kDa. The protein is highly similar to acyl-CoA desaturases from Drosophila melanogaster to Homo sapiens. The catalytically essential histidine clusters and the potential transmembrane domains are well conserved.

Impact of Radiation and Chemotherapy on Risk of Dental Abnormalities A Report From the Childhood Cancer Survivor Study

The current study was performed to describe frequencies and risk factors of altered oral health and odontogenesis in childhood cancer survivors.

Possible localization of a major gene for cleft lip and palate to 4q

Two of the 13 PCR markers were most informative in tentatively identifying a major gene for cleft lip on the q arm of chromosome #4 with a maximum LOD score of 2.27 (Ø= 0)

Accuracy and precision of a 3D anthropometric facial analysis with and without landmark labeling before image acquisition

OBJECTIVE To determine the influence of landmark labeling on the accuracy and precision of an indirect facial anthropometric technique. MATERIALS AND METHODS Eighteen standard linear craniofacial measurements were obtained from 10 adults using the 3dMDface system, with landmarks labeled (Labeled_3D) and without landmarks labeled (Unlabeled_3D) before image acquisition, and these were compared with direct anthropometry (Caliper). Images were acquired twice in two different sessions 1 week apart (T1 and T2). Accuracy and precision were determined by comparing mean measurement values and absolute differences between the three methods. RESULTS Mean measurements derived from three-dimensional (3D) images and direct anthropologic measurements were mostly similar. However, statistically significant differences (P < .01) were noted for seven measurements in Labeled_3D and six measurements in Unlabeled_3D. The magnitudes of these differences were clinically insignificant (<2 mm). In terms of precision, results demonstrated good reproducibility for both methods, with a tendency toward more precise values in Labeled_3D, when compared with the other two techniques (P < .05). We found that Labeled_3D provided the most precise values, Unlabeled_3D produced less precise measurements, and Caliper was the least capable of generating precise values. CONCLUSIONS Overall, soft tissue facial measurement with the 3dMDface system demonstrated similar accuracy and precision with traditional anthropometry, regardless of landmarking before image acquisition. Larger disagreements were found regarding measurements involving ears and soft tissue landmarks without distinct edges. The 3dMDface system demonstrated a high level of precision, especially when facial landmarks were labeled.

Genomewide Scan for Nonsyndromic Cleft Lip and Palate in Multigenerational Indian Families Reveals Significant Evidence of Linkage at 13q33.1-34

Nonsyndromic cleft lip with or without cleft palate (CL-P) is a common congenital anomaly with incidence ranging from 1 in 300 to 1 in 2,500 live births. We analyzed two Indian pedigrees (UR017 and UR019) with isolated, nonsyndromic CL-P, in which the anomaly segregates as an autosomal dominant trait. The phenotype was variable, ranging from unilateral to bilateral CL-P. A genomewide linkage scan that used approximately 10,000 SNPs was performed. Nonparametric linkage (NPL) analysis identified 11 genomic regions (NPL>3.5; P<.005) that could potentially harbor CL-P susceptibility variations. Among those, the most significant evidence was for chromosome 13q33.1-34 at marker rs1830756 (NPL=5.57; P=.00024). This was also supported by parametric linkage; MOD score (LOD scores maximized over genetic model parameters) analysis favored an autosomal dominant model. The maximum LOD score was 4.45, and heterogeneity LOD was 4.45 (alpha =100%). Haplotype analysis with informative crossovers enabled the mapping of the CL-P locus to a region of approximately 20.17 cM (7.42 Mb) between SNPs rs951095 and rs726455. Thus, we have identified a novel genomic region on 13q33.1-34 that harbors a high-risk variant for CL-P in these Indian families.

The lineage-specific gene ponzr1 is essential for zebrafish pronephric and pharyngeal arch development

The Homeobox (Hox) and Paired box (Pax) gene families are key determinants of animal body plans and organ structure. In particular, they function within regulatory networks that control organogenesis. How these conserved genes elicit differences in organ form and function in response to evolutionary pressures is incompletely understood. We molecularly and functionally characterized one member of an evolutionarily dynamic gene family, plac8 onzin related protein 1 (ponzr1), in the zebrafish. ponzr1 mRNA is expressed early in the developing kidney and pharyngeal arches. Using ponzr1-targeting morpholinos, we show that ponzr1 is required for formation of the glomerulus. Loss of ponzr1 results in a nonfunctional glomerulus but retention of a functional pronephros, an arrangement similar to the aglomerular kidneys found in a subset of marine fish. ponzr1 is integrated into the pax2a pathway, with ponzr1 expression requiring pax2a gene function, and proper pax2a expression requiring normal ponzr1 expression. In addition to pronephric function, ponzr1 is required for pharyngeal arch formation. We functionally demonstrate that ponzr1 can act as a transcription factor or co-factor, providing the first molecular mode of action for this newly described gene family. Together, this work provides experimental evidence of an additional mechanism that incorporates evolutionarily dynamic, lineage-specific gene families into conserved regulatory gene networks to create functional organ diversity.

Craniofacial and intraoral phenotype of Robinow syndrome forms

Beiraghi S, Leon‐Salazar V, Larson BE, John MT, Cunningham ML, Petryk A, Lohr JL. Craniofacial and intraoral phenotype of Robinow syndrome forms.

The effect of stannous and sodium fluoride on coronal caries, root caries and bone loss in rice rats

Sixty rice rats (Oryzomys palustris) were divided by littermate into 3 groups of 20 each. The 3 groups received either SnF2 (1000 parts/10(6) F), NaF (1000 parts/10(6] or double-distilled water (control). Test solutions were topically applied to molar teeth, twice daily, for 7 days. All rats were also provided with double-distilled drinking water and diet 2000 ad libitum. Experiments ended after 9 weeks. Alveolar bone loss, root and coronal caries were recorded and scored. SnF2 significantly reduced bone loss (p less than 0.05), but NaF did not. Root caries was significantly different in all 3 groups (p less than 0.05). SnF2 and NaF both reduced coronal caries significantly (p less than 0.05) in comparison to the control. However, the fluoride groups were not significantly different from each other. SnF2 may influence root caries via remineralization and an antimicrobial effect of the stannous ion.