Deep Phenotyping and Genetic Characterization of a Cohort of 70 Individuals With 5p Minus Syndrome

Chromosome-5p minus syndrome (5p-Sd, OMIM #123450) formerly known as Cri du Chat syndrome results from the loss of genetic material at the distal region of the short arm of chromosome 5. It is a neurodevelopmental disorder of genetic cause. So far, about 400 patients have been reported worldwide. Individuals affected by this syndrome have large phenotypic heterogeneity. However, a specific phenotype has emerged including global developmental delay, microcephaly, delayed speech, some dysmorphic features, and a characteristic and monochromatic high-pitch voice, resembling a cat’s cry. We here describe a cohort of 70 patients with clinical features of 5p- Sd characterized by means of deep phenotyping, SNP arrays, and other genetic approaches. Individuals have a great clinical and molecular heterogeneity, which can be partially explained by the existence of additional significant genomic rearrangements in around 39% of cases. Thus, our data showed significant statistical differences between subpopulations (simple 5p deletions versus 5p deletions plus additional rearrangements) of the cohort. We also determined significant “functional” differences between male and female individuals.

ABORDAGEM FISIOTERAPÊUTICA PELO CONCEITO NEUROEVOLUTIVO BOBATH NA SÍNDROME CRI DU CHAT: ESTUDO DE CASO

Cri du Chat Syndrome (CDCS) is a genetic disease that results from an extremely small deletion (5p15.2) or a deletion of the entire short arm of the chromosome (5p). It is a rare disease, with an incidence of 1/15000 to 1/50000 live births, with a higher prevalence in females. The clinical manifestations are characterized by typical crying, known as meowing of cat, inferior deviation of the extremities of the lips, rounded face, height and weight below the standards, wide nasal bridge, epicanthic folds, ears with low implantation, hypotonia, hypertelorism, microretrognatism and delayed psycho-motor development. The treatment is based on early rehabilitation, in which physiotherapy works to prevent complications and to correct deformities. Thus, the objective of this study was to verify the efficacy of the Bobath Concept contribution in the treatment of patients with CDCS. The case study was done with a 4-year-old female child with a confirmed diagnosis by genetic screening. The patient was submitted to the evaluation through the Denver Test and Pediatric Disability Assessment (PEDI) protocols. The intervention was performed in 20 sessions at the physical therapy clinic of ANPR in Maringá-PR, for 30 minutes, with repetitions of 2 times a week, totaling 2 months of treatment, through the Bobath Concept. Motor stimulation was performed in the patient according to their needs. The results show that the treatment through the physiotherapeutic approach, using the Bobath Concept can improve the child's motor development, promoting her independence.

A Quantitative Trait Locus on Chromosome 5p Influences D-Dimer Levels in the San Antonio Family Heart Study

Background. D-dimer is associated with increasing severity of atherosclerosis and with increased risk of a cardiovascular disease (CVD).Methods and Results. To better understand this risk factor, we performed a genome scan on 803 (301 males and 502 females) Mexican Americans in the San Antonio Family Heart Study (SAFHS). The SAFHS is ideal for the discovery of quantitative trait loci (QTLs) influencing CVD because CVD risk factors are prevalent in Mexican Americans of San Antonio and because the study design involves large families, which is optimal for QTL discovery. D-dimer levels were normalized in our study. We found that D-dimer levels were heritable, at about 23% heritability (P≈.00001). In a linkage analysis employing 432 microsatellite markers, we found strong evidence of a QTL on chromosome 5p with a lod score of 3.32 at 21 centiMorgans (cM). We also found suggestive evidence of a QTL on chromosome 2q with a lod score of 2.33 at 207 cM.Conclusions. To our knowledge, the putative QTL on chromosome 5p is novel. The possible QTL on chromosome 2q is discussed in relation to a recent report of linkage of a related hemostatic factor to the same location. These results warrant further investigation.

Chromosome 5p Region SNPs Are Associated with Risk of NSCLC among Women

In a population-based case-control study, we explored the associations between 42 polymorphisms in seven genes in this region and non-small cell lung cancer (NSCLC) risk among Caucasian (364 cases; 380 controls) and African American (95 cases; 103 controls) women. TwoTERTregion SNPs, rs2075786 and rs2853677, conferred an increased risk of developing NSCLC, especially among African American women, andTERT-rs2735940 was associated with a decreased risk of lung cancer among African Americans. Five of the 20GHRpolymorphisms andSEPP1-rs6413428 were associated with a marginally increased risk of NSCLC among Caucasians. Random forest analysis reinforced the importance ofGHRamong Caucasians and identifiedAMACR, TERT, andGHRamong African Americans, which were also significant using gene-based risk scores. Smoking-SNP interactions were explored, and haplotypes inTERTandGHRassociated with NSCLC risk were identified. The roles ofTERT, GHR, AMACRandSEPP1genes in lung carcinogenesis warrant further exploration.