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LBR (Lamin B Receptor) encodes a bifunctional protein important for cholesterol biosynthesis and heterochromatin organization on the inner nuclear membrane. Pathogenic variants in LBR are associated with marked phenotypic variability, ranging from the benign Pelger-Huet anomaly to lethal Greenberg Dysplasia. We performed trio exome sequencing (ES) on two patients with atypical variants of skeletal dysplasia and their unaffected parents. Patient 1 exhibited frontal bossing, mid-face hypoplasia, short stature with rhizomelic limb shortening, and relative macrocephaly at birth. Although remained short, Patient 1 later showed spontaneous improvement in her skeletal findings. Exome sequencing revealed two novel variants in LBR, c.1504C > G (p.Arg502Gly) in exon 12 and c.1748G > T (p.Arg583Leu) in exon 14, which were inherited from her unaffected father and mother, respectively. Sterol analysis revealed an increased level of cholesta‑8,14‑dien‑3β‑ol to 2.9% of total sterols, consistent with a functional deficiency of 3β‑hydroxysterol Δ14‑reductase. Patient 2 presented at birth with short stature and marked rhizomelic limb shortening but later exhibited decreasing severity of shortening of the long bones and improvement in the radiographic skeletal abnormalities although he continued to be significantly short at age 10 years. Exome sequencing revealed that Patient 2 is homozygous for a pathogenic variant c.1534C > T (p.Arg512Trp) in exon 12 of LBR, which was inherited from his unaffected consanguineous parents. This report provides further evidence for a phenotypic spectrum of LBR-associated disorders and expands the genotypic spectrum by describing 3 novel disease-causing variants that have not been previously associated with a disease. Moreover, our data on Patient 1 demonstrate that variants throughout the gene appear to influence both the sterol reductase and nuclear functions of LBR.

Purpose Primary congenital glaucoma (PCG) accounts for 26–29% of childhood blindness in Egypt. The identification of disease causing mutations has not been extensively investigated. We aimed to examine the frequency of CYP1B1 and MYOC mutations in PCG Egyptian patients, and study a possible genotype/phenotype correlation. Methods Ninety-eight patients with PCG diagnosed at the Ophthalmology department of Alexandria Main University Hospital were enrolled. Demographic and phenotypic characteristics were recorded. Patients and 100 healthy subjects (control group) were screened for two mutations in CYP1B1 gene (G61E, R368H) and one mutation in MYOC gene (Gln48His) using polymerase chain reaction/restriction fragment length polymorphism (PCR/RFLP). Phenotypic characteristics pertaining to disease severity were compared. Results Nineteen patients (19%) with PCG were found positive for one or more of the mutations screened for. Seven patients (7%) were homozygous for the G61E mutation. Ten patients (10%) were heterozygous; 6 for the G61E mutation, 2 for the R368H mutation and 2 for the Gln48His mutation. Two patients (2%) were double heterozygotes harboring a R368H as well as a Gln48His mutation. The most common mutation observed was the G61E in 13 patients; 7 homozygotes and 6 heterozygotes for the mutation. The control group were negative for all mutations screened for. No significant correlations between the mutations and phenotype severity were detected. A statistically significant positive correlation however was found between the different mutations and each of the IOP and the cup/disk ratio. Conclusion The current study further endorses the role of CYP1B1 mutations in the etiology of PCG among Egyptian patients and is the first study to report MYOC gene mutation in Egyptian patients with PCG.

Purpose To investigate for the first time in Egypt and the Middle East the relationship between a specific gene and the presence of severely resorbed edentulous mandibular ridges in a sample of the Egyptian population. Materials and methods The study was conducted on 50 subjects divided into case and control groups according to the residual ridge height. Saliva was used as a convenient source of DNA in the dental clinic. A certain genetic variation (1772C>T) in an important gene related to bone healing (hypoxia-inducible factor-1 alpha [HIF1-α] gene) was selected. The genetic variation 1772C>T is a single nucleotide polymorphism (SNP) that occurs when corresponding sequences of DNA from different individuals differ at one base. Then, we have 2 forms of the gene (2 alleles): C and T. SNPs typically have 3 genotypes; in this study, they are the CC, CT, and TT genotypes. Polymerase chain reaction (PCR) restriction fragment length polymorphism (RFLP) was the method performed for genotyping. The statistical significance of the results was evaluated by the Chi-square test and Fisher Exact test. Results A statistically significant difference in the distribution of the TT genotype between both groups was detected with p-value = 0.049. There was also a difference in the distribution of the CC and CT genotypes, but it was not statistically significant, since the p-values were 0.733 and 0.145, respectively. The T alleles were more abundant in the case group, while the control group showed more frequency of the C allele with no statistical significance. Conclusion The TT genotype of the 1772C>T polymorphism of HIF1-α gene is related to the presence of severely atrophied residual ridges in completely edentulous Egyptians. This can be used as a marker to predict the future condition of the ridge using saliva samples. Further studies on larger scale are recommended.

Background and aim: Fraser syndrome (FS) is a rare autosomal recessive disorder characterized by cryptophthalmos, cutaneous syndactyly, laryngeal malformations and urogenital defects. It may be also associated with ear, nose and skeletal abnormalities. There is a marked interfamilial clinical variability. However, there is strong phenotypic similarity and concordance of the degree of severity of the disease within a family. Our aim was to report new cases of FS from the Egyptian population. Patients and methods: The study was carried out on 6 new cases of FS from four Egyptian families. All patients satisfied the diagnostic criteria for FS. Results: Cryptophthalmos and ambiguous genitalia were each present in 5/6 of the studied cases, while syndactyly and urinary tract abnormalities were found in 4/6 of them. Nasal anomalies, sclerocornea and abnormal hair growth pattern were constant features observed in 100% of the cases. The frequency of additional anomalies in our series was also higher than those previously reported as umbilical abnormalities and contractures of large joints. Conclusion: In conclusion, our findings add further evidence for the clinical variability associated with FS. The studied cases showed inconsistent compatibility with life and variable expressions in prenatal sonographic findings and postnatal clinical manifestations. Keywords: Fraser syndrome; Cryptophthalmos; Syndactyly; Renal agenesis; Laryngeal malformations; Urogenital defects; Egypt