CASE REPORT: Her peripheral smear and bone marrow aspirate showed many myeloblasts. Chromosomal study revealed t(8;22;21)(q22;q12;q22) and loss of X chromosome. Fluorescence in situ hybridization (FISH) using whole chromosome painting probes confirmed the three-way translocation involving chromosomes 8, 21 and 22. RUNX1-RUNX1T1 rearrangement was identified in FISH and reverse transcriptase polymerase chain reaction confirming the diagnosis of AML with variant t(8;21). The patient was treated with standard chemotherapy. She achieved morphological remission one month after induction chemotherapy.
DISCUSSION: Although the clinical significance of variant t(8;21) is not well delineated, the evaluation of 31 such cases suggests patients with variant t(8;21) have similar prognosis to those with classical t(8;21).
METHOD: Whole-genome sequencing (WGS) was performed in seven early-age-onset Malay CRC patients. Potential germline genetic variants, including single-nucleotide variations and insertions and deletions (indels), were prioritized using functional and predictive algorithms.
RESULTS: An average of 3.2 million single-nucleotide variations (SNVs) and over 800 indels were identified. Three potential candidate variants in three genes-IFNE, PTCH2 and SEMA3D-which were predicted to affect protein function, were identified in three Malay CRC patients. In addition, 19 candidate genes-ANKDD1B, CENPM, CLDN5, MAGEB16, MAP3K14, MOB3C, MS4A12, MUC19, OR2L8, OR51Q1, OR51AR1, PDE4DIP, PKD1L3, PRIM2, PRM3, SEC22B, TPTE, USP29 and ZNF117-harbouring nonsense variants were prioritised. These genes are suggested to play a role in cancer predisposition and to be associated with cancer risk. Pathway enrichment analysis indicated significant enrichment in the olfactory signalling pathway.
CONCLUSION: This study provides a new spectrum of insights into the potential genes, variants and pathways associated with CRC in Malay patients.
AIMS: (1) To investigate the association between birth weight and anthropometric measurements during adulthood; (2) to study the genetic and environmental influences on body measures including birth weight, weight and height among twins; and (3) to assess the variation in heritability versus environment among two cohorts of twins who lived in different geographical areas.
SUBJECTS AND METHODS: Twins were collected from two twin registers. Data on birth weight, adult weight and height in 430 MZ and 170 DZ twins living in two geographically distinct parts of the world were collected. A genetic analysis was performed using MX software.
RESULTS: Birth weight was associated with weight, height and BMI. Both MZ and DZ twins with low birth weight had shorter height during their adult life (p = 0.001), but only MZ twins with lower birth weight were lighter at adulthood (p = 0.001). Intra-pair differences in birth weight were not associated with differences in adult height (p = 0.366) or weight (p = 0.796). Additive genetic effects accounted for 53% of the variance in weight, 43% in height and 55% in birth weight. The remaining variance was attributed to unique environmental effects (15% for weight, 13% for height and 45% for birth weight and only 16% for BMI). Variability was found to be different in the two cohorts. The best fitting model for birth weight and BMI was additive genetic and non-shared environment and for weight and height was additive genetic, non-shared environment (plus common Environment).
CONCLUSIONS: Data suggests that the association between weight at birth and anthropometric measures in later life is influenced by both genetic and environmental factors. Living in different environments can potentially relate to variation found in the environment.