Batten disease is a rare, progressive neurogenetic disorder composed of 13 genotypes that often presents in childhood. Children present with seizures, vision loss, and developmental regression. Neuror Show more
Batten disease is a rare, progressive neurogenetic disorder composed of 13 genotypes that often presents in childhood. Children present with seizures, vision loss, and developmental regression. Neurorehabilitation services (i.e., physical therapy, occupational therapy, and speech-language therapy) can help improve the quality of life for children and their families. Owing to the rarity of Batten disease, there are no standardized clinical recommendations or outcome assessments. To describe developmental profiles, current dose of neurorehabilitation, and outcome assessments used clinically for children diagnosed with Batten disease. Electronic medical records of 70 children with Batten disease (subtypes n = 5 CLN1; n = 25 CLN2; n = 23 CLN3; n = 17 CLN6) were reviewed (7.0 ± 3.4 years). Descriptive statistics were used to describe clinical features, developmental skills, dose of neurorehabilitation, and outcome assessment use. Across CLN subtypes, most children experienced vision impairments (61%) and seizures (68%). Most children demonstrated delays in fine motor (65%), gross motor (80%), cognitive (63%), and language skills (83%). The most common frequency of neurorehabilitation was weekly (42% to 43%). Two standardized outcome assessments were used to track developmental outcomes: Peabody Developmental Motor Scales, second edition (30% of children completed this assessment) and Preschool Language Scales, fifth edition (27.4% of children completed this assessment). Neurorehabilitation professionals should understand the clinical features and prognosis for children with Batten disease. The child's clinical features and family preferences should guide the rehabilitation plan of care. Future work needs to be completed to define dosing parameters and validate outcome assessments for neurorehabilitation services. Show less
Postprandial lipemia (PPL) is an important risk factor for cardiovascular disease. Inter-individual variation in the dietary response to a meal is known to be influenced by genetic factors, yet genes Show more
Postprandial lipemia (PPL) is an important risk factor for cardiovascular disease. Inter-individual variation in the dietary response to a meal is known to be influenced by genetic factors, yet genes that dictate variation in postprandial lipids are not completely characterized. Genetic studies of the plasma lipidome can help to better understand postprandial metabolism by isolating lipid molecular species which are more closely related to the genome. We measured the plasma lipidome at fasting and 6 h after a standardized high-fat meal in 668 participants from the Genetics of Lipid-Lowering Drugs and Diet Network study (GOLDN) using ultra-performance liquid chromatography coupled to (quadrupole) time-of-flight mass spectrometry. A total of 413 unique lipids were identified. Heritable and responsive lipid species were examined for association with single-nucleotide polymorphisms (SNPs) genotyped on the Affymetrix 6.0 array. The most statistically significant SNP findings were replicated in the Amish Heredity and Phenotype Intervention (HAPI) Heart Study. We further followed up findings from GOLDN with a regional analysis of cytosine-phosphate-guanine (CpGs) sites measured on the Illumina HumanMethylation450 array. A total of 132 lipids were both responsive to the meal challenge and heritable in the GOLDN study. After correction for multiple testing of 132 lipids (α = 5 × 10 Show less
Nearly 10% of all pancreatic cancer (PCA) results from genetic predisposition. Although abnormalities in sporadic PCA have been described, little is known about the genetics of heritable PCA. The purp Show more
Nearly 10% of all pancreatic cancer (PCA) results from genetic predisposition. Although abnormalities in sporadic PCA have been described, little is known about the genetics of heritable PCA. The purpose of this study was to identify novel genes expressed in patients with a presumed genetic predisposition or "familial" PCA. We defined "familial" PCA as patients having one or more first-degree relatives with biopsy-proven adenocarcinoma of the pancreas. Using a PCR-based subtractive and enrichment procedure, representational difference analysis (RDA), pancreatic tumor cDNA was reverse-transcribed from pooled poly(A)+ mRNA from six such patients (tester) and compared to pooled cDNA from five normal pancreata (driver). Tumor-specific gene fragments were identified and confirmed to be overexpressed in familial PCA by comparative RT-PCR. Six PCA cell lines, 11 sporadic tumors, 5 neuroendocrine tumors, and 3 chronic pancreatitis tissues were screened to determine the specificity of these genes. Sequence analysis revealed several sequences of unknown significance and six genes previously described in neoplasia/carcinogenesis: Apolipoprotein A4, CEA, Keratin 19, Stratifin (14-3-3 sigma), Trefoil Factor, and Calcium Binding Protein S100 A6. Screening of cell lines and pancreatic tissue types showed varying degrees of specificity for familial and sporadic PCA. The APO-A4 gene was up-regulated in familial PCA. The pattern of frequency in all screened tissue suggests that these genes are associated with conditions that produce significant desmoplastic responses and are difficult to differentiate from chronic inflammatory processes. Apolipoprotein A4 is preferentially expressed in familial patients, suggesting that the importance of fatty acid synthesis in carcinogenesis be investigated further. Show less