Methods: Lymphocyte subset enumeration test and whole exome sequencing were performed.
Results: We identified a compound heterozygous CR2 mutation (c.1916G>A and c.2012G>A) in both patients. These variants were then confirmed using Sanger sequencing.
Conclusion: Whole exome sequencing analysis of the monozygotic twins revealed compound heterozygous missense mutations in CR2.
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.
METHOD: A case series.
RESULTS: We present a case series of juvenile myasthenia gravis in a tertiary centre in Malaysia. Two of the three cases consist of a pair of twins who presented with ptosis of bilateral eyes; the first twin presented 4 months later than the second twin. These two cases were positive for anti-acetylcholine receptor antibodies and had generalized myasthenia gravis, whereas the other case was negative for receptor antibodies and was purely ocular myasthenia gravis.
CONCLUSION: Juvenile myasthenia gravis is relatively rare in toddlers. Early diagnosis and commencement of treatment is important to slow the progression of the disease and avoiding life-threatening events.
CASE PRESENTATION: This is a rare case of a pair of 8-year-old monochorionic diamniotic identical twin, who on family cascade screening were diagnosed as definite FH, according to the Dutch Lipid Clinic Criteria (DLCC) with a score of 10. There were no lipid stigmata noted. Baseline lipid profiles revealed severe hypercholesterolaemia, (TC = 10.5 mmol/L, 10.6 mmol/L; LDL-c = 8.8 mmol/L, 8.6 mmol/L respectively). Their father is the index case who initially presented with premature CAD, and subsequently diagnosed as FH. Family cascade screening identified clinical FH in other family members including their paternal grandfather who also had premature CAD, and another elder brother, aged 10 years. Genetic analysis by targeted next-generation sequencing using MiSeq platform (Illumina) was performed to detect mutations in LDLR, APOB100, PCSK9, ABCG5, ABCG8, APOE and LDLRAP1 genes. Results revealed that the twin, their elder brother, father and grandfather are heterozygous for a missense mutation (c.530C > T) in LDLR that was previously reported as a pathogenic mutation. In addition, the twin has heterozygous ABCG8 gene mutation (c.55G > C). Their eldest brother aged 12 years and their mother both had normal lipid profiles with absence of LDLR gene mutation.
CONCLUSION: A rare case of Asian monochorionic diamniotic identical twin, with clinically diagnosed and molecularly confirmed heterozygous FH, due to LDLR and ABCG8 gene mutations have been reported. Childhood FH may not present with the classical physical manifestations including the pathognomonic lipid stigmata as in adults. Therefore, childhood FH can be diagnosed early using a combination of clinical criteria and molecular analyses.