An eight-case 1q21 region series: novel aberrations and clinical variability with new features.

BACKGROUND: Rearrangement of the 1q21 region of chromosome 1 manifests as multiple phenotypes, including microcephaly, intellectual disability, dysmorphic facial features, eye abnormalities, cardiac defects, genitourinary anomalies, autism spectrum disorder, psychiatric conditions and seizures. Herein, we describe eight patients with 1q21 deletion and duplication syndromes, and novel deletions and findings. METHODS: Chromosomal microarray analysis was performed to identify the existence of copy number variation. Quantitative polymerase chain reaction was applied using specific primers for the control and 1q21 region of chromosome 1. Mutational analysis was performed in case 5 using direct genomic sequencing for exons 1-6 in RBM8A. RESULTS: Copy number variation analysis identified seven deletions and one duplication of the 1q21 region in the eight patients. In addition, four variations were de novo, and two deletions are reported here for the first time. One of the cases (case 7) presents moderate intellectual disability and dysmorphic facial findings, whereas chromosomal microarray analysis showed that case 7 had an 889-kb deletion in the 1q21 proximal region (GPR89A, PDZK1, CD160, POLR3C and NBPF12). CONCLUSION: Although the deletion in case 5 did not include the thrombocytopenia-absent radius syndrome critical region or the RBM8A gene, he had pectoral muscle hypoplasia, radius and humerus hypoplasia and short curved ribs, which are indicative of a potential thrombocytopenia-absent radius region modifier. The findings in case 7 suggest that the proximal part of the 1q21 microdeletion syndrome region might be very important for the onset of clinical manifestations. Some novel findings were observed in the presented cases, such as radius and humerus hypoplasia and brain stem hypoplasia. The presented findings expand the spectrum of 1q21 aberrations and provide evidence of genotype-phenotype correlations for this region.

OCULOECTODERMAL SYNDROME: A NEW CASE WITH GIANT CELL GRANULOMAS AND NON-OSSIFYING FIBROMAS.

Oculoectodermal syndrome (OES) is a very rare disorder with an unknown etiology and characterized by aplasia cutis congenita, epibulbar dermoid and hyperpigmentation areas on the skin. To the best of our knowledge, two cases of OES have been reported to date with recurrent giant cell granuloma in the jaw and one of them also had a non-ossified fibroma in the long bones. Herein, we report the second case with aplasia cutis congenita, epibulbar dermoid, hyperpigmentation along Blaschko lines and also giant cell granuloma in the jaw and non-ossified fibromas in the bones.

A patient with 9q subtelomeric deletion syndrome with additional findings.

We describe a one-year old girl, with a de novo segmental aneusomy due to the subtelomeric deletion of the long arm of chromosome 9, determined via fluorescence in situ hybridization technique. Common clinical findings of the 9q subtelomeric deletion syndrome are developmental delay, hypotonia, microcephaly and dysmorphic facial features especially including midface hypoplasia and low set ears. Sensorineural deafness, as a rare condition of the syndrome is also announced. Presented case with sensorineural deafness has most of the common clinical findings of the syndrome, except brachycephaly, downslanting palpebral fissures, synophrys, epicanthus and low set ears, and has also additional findings like microtia, asymmetric and simple ears, long curly eyelashes and fetal finger pads which are not reported previously.

Occupational health of Turkish Aegean small-scale fishermen.

BACKGROUND: Fishing has always been a dangerous occupation, and numerous factors have a direct or indirect impact on the health of fisherman. AIMS: To examine the health, safety and working conditions of small-scale fishing fleets in the Turkish Aegean Sea coasts. METHODS: Data were obtained from a questionnaire distributed to a random sample of small-scale fishermen along the Aegean Sea coast. Data collection took place between September 2009 and January 2010. RESULTS: Out of 5714 Aegean Sea small-scale fishermen, 1166 from 76 fishing ports participated. Twenty-nine per cent of fishermen did not have any social security cover. The most prevalent health problems (using International Classification of Diseases and Related Health Problems 10th Revision [ICD-10]) found were musculoskeletal problems (e.g. discopathies, muscular strain, rheumatism) and eye, ear-nose, digestive and urinary system problems. Alcohol consumption was high (68%) in fishermen and 72% reported that they smoked more during fishing trips. Health problems appeared to be associated with a number of factors including migrant status, income satisfaction, rank, type of fishing and cumulative work per year. CONCLUSIONS: In Turkey, small-scale fishermen experience a significant number of health problems and have unhealthy lifestyles. Interventions designed to improve working conditions of small-scale fishermen could help to reduce the number of occupational injuries, which in turn may impact positively on their health. Prevention policies to reduce alcohol and tobacco consumption should also be developed.

Linkage analysis and a novel COL4A5 mutation in a large Turkish family with Alport syndrome.

BACKGROUND: Alport syndrome (AS) is a renal disease that is characterized by proteinuria and progressive renal failure, and often accompanied by sensorineural hearing loss and ocular changes. Mutations in the genes encoding for three members of the type IV collagen protein family have been found to be the cause of the disease. We describe a large Turkish family with X-linked AS. We performed linkage analysis in this family and sequencing to identify the mutation in the proband whose disease was confirmed by renal biopsy. METHODS: After genomic DNAs extracted, linkage to the COL4A5 locus was examined using the 2B6 and 2B20, DXS1106, DXS1105 and COL4A5 markers. In addition, COL4A5 gene sequence analysis was performed in the proband. RESULTS: Genetic linkage analysis demonstrated co-segregation of the disease. Haplotype analysis showed that the same haplotype was carried by all affected males and obligatory carrier females. Mutation analysis of the proband has revealed a novel nonsense mutation (c.1135C>T; Gln379X) in exon 19 of the COL4A5 gene which may lead to a more severe phenotype in affected family members carrying this mutation. According to GenBank data base, this mutation has not been reported previously. CONCLUSION: Genetic testing identified a previously undescribed COL4A5 mutation as the cause of the disease.