Ehlers-Danlos syndrome (EDS) describes a group of clinical entities in which the connective tissue, primarily that of the skin, joint and vessels, is abnormal, although the resulting clinical manifestations can vary widely between the different historical subtypes. Many cases of hereditary disorders of connective tissue that do not seem to fit these historical subtypes exist. The aim of this study is to describe a large series of patients with inherited connective tissue disorders evaluated by our clinical genetics service and for whom a likely causal variant was identified. In addition to clinical phenotyping, patients underwent various genetic tests including molecular karyotyping, candidate gene analysis, autozygome analysis, and whole-exome and whole-genome sequencing as appropriate. We describe a cohort of 69 individuals representing 40 families, all referred because of suspicion of an inherited connective tissue disorder by their primary physician. Molecular lesions included variants in the previously published disease genes B3GALT6, GORAB, ZNF469, B3GAT3, ALDH18A1, FKBP14, PYCR1, CHST14 and SPARC with interesting variations on the published clinical phenotypes. We also describe the first recessive EDS-like condition to be caused by a recessive COL1A1 variant. In addition, exome capture in a familial case identified a homozygous truncating variant in a novel and compelling candidate gene, AEBP1. Finally, we also describe a distinct novel clinical syndrome of cutis laxa and marked facial features and propose ATP6V1E1 and ATP6V0D2 (two subunits of vacuolar ATPase) as likely candidate genes based on whole-genome and whole-exome sequencing of the two families with this new clinical entity. Our study expands the clinical spectrum of hereditary disorders of connective tissue and adds three novel candidate genes including two that are associated with a highly distinct syndrome.

Klippel-Feil syndrome (KFS) is a segmentation malformation of the cervical spine; clinically, it manifests as a short neck with reduced mobility and a low posterior hairline. Several genes have been proposed as candidates for KFS when it is present with other associated anomalies, but the genetics of isolated KFS have been difficult to study because of the syndrome's mostly sporadic occurrence. We describe a multiplex consanguineous family in which isolated KFS maps to a single 17q21.31 locus that harbors a homozygous frameshift deletion in MEOX1; this deletion results in complete instability of the transcript. Direct sequencing of this gene in two siblings from another consanguineous family affected by isolated KFS uncovered another homozygous truncating (nonsense) MEOX1 mutation that also leads to complete degradation of the transcript. This gene encodes a transcription factor with a well-established and nonredundant role in somite development, and homozygous null alleles of Meox1 in mice have a cervical skeletal defect that is remarkably similar to the one we observe in human individuals with MEOX1 mutations. Our data strongly suggest that KFS is the human phenotypic equivalent of the sclerotome polarity defect that results from Meox1 deficiency in mice.

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Objectives: To quantify the prevalence and identify the associated factors of musculoskeletal pain among Saudi female school teachers. Methods: An observational quantitative cross-sectional survey of female Saudi school teachers in five different areas of Saudi Arabia was carried out between August and October 2013. A self-administered questionnaire was used in which the items related to participants’ demographic information and pain information were included. A numeric pain rating scale was used for patient self-reporting of pain. Data analysis was carried out using SPSS Pc+ version 21.0 statistical software. Results: Four hundred and eighty six female school teachers responded to the survey. Severe Low back pain was reported by 38.1% of teacher, followed by knee pain (26.3%), heel (24.1%), shoulder (20.6%), upper back (17.7%), hip joint (16.5%),ankle (12.3%), neck (11.3%). Sever pain of elbow (5.6%) and wrist (7.4%) was the least reported. Pain affected work at school in 46.1% of school teachers. A combination of variables: body mass index, Vitamin D deficiency, teaching level, presence of chronic illness, were found to be significantly associated with musculoskeletal pain. Conclusion: The results of self-reported prevalence of musculoskeletal pain among female Saudi school teachers is useful to educate the school teachers for adequate care so as to prevent these pains. There is a need for the higher authorities to address this issue and implement intervention programs to alleviate the pain and suffering of these school teachers.