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Grossly delayed graft function in a living related kidney transplant recipient: a case report

Thye YL, Lim SK, Wong CM, Keng TC, Chong YB, Tan SY

Transplant Proc, 2008 Sep;40(7):2435-6.
PMID: 18790259 DOI: 10.1016/j.transproceed.2008.07.051

Delayed graft function is a potentially challenging problem especially in cadaveric kidney transplant recipients. It adversely impacts long-term graft survival. It is rarely seen in living kidney transplants. Recovery of graft function usually occurs within a month. The chances of recovery of graft function diminish with further prolongation of delayed function. In fact, recovery of graft function after 3 months has rarely been described, we report herein recovery of graft function after 132 days of nonfunction in a living related kidney transplant.

Matched MeSH terms: Siblings
Predictors of the yield of mobilized peripheral blood CD34+ cells in HLA-matched sibling donor

Fadilah SA, Mohd-Razif MI, Seery ZA, Nor-Rafeah T, Wan-Fariza WJ, Habsah A, et al.

Transfus Apher Sci, 2013 Dec;49(3):583-9.
PMID: 24012241 DOI: 10.1016/j.transci.2013.07.032

We examined the donor factors that may affect the yield of peripheral blood stem cell (PBSC) mobilized from healthy donors. Pre-apheresis PB-CD34(+) cell count was the only factor that correlated with PBSC yield. Leukocyte count (LC) and monocyte count (MC) correlated with PB-CD34(+) cell. Male gender and PB-CD34(+) cell count of at least 87.1/μL and 69.8/μL on day-4 and -5 of G-CSF were associated with the ability to harvest at least 5×10(6)/kg CD34(+) cells after one apheresis. We concluded that gender and PB-CD34(+) cell count are important predictors of PBSC yield. LC and MC may serve as surrogate markers for estimating the PB-CD34(+) cell count.

Matched MeSH terms: Siblings
Fulltext A rare X-linked inherited mucocutaneous syndrome in two siblings

Chong LA, Ariffin H

Med J Malaysia, 2009 Dec;64(4):327-9.
PMID: 20954562 MyJurnal

We report on an 11 year-old boy with dyskeratosis congenita who presented with dystrophic nails, dysphagia, hyperpigmentation and oral leukoplakia. He had a brother who died 14 years earlier with similar presenting symptoms and aplastic anaemia. Genetic studies of our patient demonstrated the presence of a DKC1 mutation and confirmed our diagnosis. Further genetic screening revealed that his mother and one of his four sisters are heterozygous for the same mutation.

Matched MeSH terms: Siblings
Phenotypic variation among siblings with arrhythmogenic right ventricular cardiomyopathy

Oon YY, Koh KT, Khaw CS, Mohd Amin NH, Ong TK

Med J Malaysia, 2019 08;74(4):328-330.
PMID: 31424042

Arrhythmogenic right ventricular cardiomyopathy (ARVC) is primarily a familial disease with autosomal dominant inheritance. Incomplete penetrance and variable expression are common, resulting in broad disease spectrum. Three patterns of phenotypic expression have been described: (1) "classic" subtype, with predominant right ventricle involvement, (2) "left dominant" subtype, with early and dominant left ventricle involvement, and (3) "biventricular" subtype, with both ventricles equally affected. Genotypephenotype associations have been described, but there are other genetic and non-genetic factors that can affect disease expression. We describe two different phenotypic expressions of ARVC in a family.

Matched MeSH terms: Siblings*
Hb lepore/β0-thalassaemia with α+-thalassaemia interactions, a potential diagnostic pitfall

Alauddin H, Mohamad Nasir S, Ahadon M, Raja Sabudin RZ, Ithnin A, Hussin NH, et al.

Malays J Pathol, 2015 Dec;37(3):287-92.
PMID: 26712677

Haemoglobin (Hb) Lepore is a variant Hb consisting of two α-globin and two δβ-globin chains. In a heterozygote, it is associated with clinical findings of thalassaemia minor, but interactions with other haemoglobinopathies can lead to various clinical phenotypes and pose diagnostic challenges. We reported a pair of siblings from a Malay family, who presented with pallor and hepatosplenomegaly at the ages of 21 months and 14 months old. The red cell indices and peripheral blood smears of both patients showed features of thalassaemia intermedia. Other laboratory investigations of the patients showed conflicting results. However, laboratory investigation results of the parents had led to a presumptive diagnosis of compound heterozygote Hb Lepore/β-thalassaemia and co-inheritance α+-thalassaemia (-α3.7). Hb Lepore has rarely been detected in Southeast Asian countries, particularly in Malaysia. These two cases highlight the importance of family studies for accurate diagnosis, hence appropriate clinical management and genetic counseling.

Matched MeSH terms: Siblings
Fulltext Factor IX mutations in haemophilia B patients in Malaysia: a preliminary study

Balraj P, Ahmad M, Khoo AS, Ayob Y

Malays J Pathol, 2012 Jun;34(1):67-9.
PMID: 22870602 MyJurnal

Haemophilia B is caused by coagulation defects in the factor IX gene located in Xq27.1 on the X chromosome. Identification of mutations contributing to defective factor IX may be advantageous for precise carrier and prenatal diagnosis. We studied 16 patients from 11 families, consisting of 8 patients of the Malay ethnic group, of which 6 were siblings. Factor IX mutations have not been previously reported in the Malay ethnic group. The functional region of the factor IX gene was sequenced and mutations were identified in either the exon or intronic regions in 15 of the patients. One novel mutation, 6660_6664delTTCTT was identified in siblings with moderate form of haemophilia B. Mutations identified in our patients when linked with disease severity were similar to findings in other populations. In summary, this preliminary data will be used to build a Malaysian mutation database which would facilitate genetic counseling.

Matched MeSH terms: Siblings
Fulltext Co-inheritance of compound heterozygous Hb Constant Spring and a single -alpha(3.7) gene deletion with heterozygous deltabeta thalassaemia: a diagnostic challenge

Azma RZ, Othman A, Azman N, Alauddin H, Ithnin A, Yusof N, et al.

Malays J Pathol, 2012 Jun;34(1):57-62.
PMID: 22870600

Haemoglobin Constant Spring (Hb CS) mutation and single gene deletions are common underlying genetic abnormalities for alpha thalassaemias. Co-inheritance of deletional and non-deletional alpha (alpha) thalassaemias may result in various thalassaemia syndromes. Concomitant co-inheritance with beta (beta) and delta (delta) gene abnormalities would result in improved clinical phenotype. We report here a 33-year-old male patient who was admitted with dengue haemorrhagic fever, with a background history of Grave's disease, incidentally noted to have mild hypochromic microcytic red cell indices. Physical examination revealed no thalassaemic features or hepatosplenomegaly. His full blood picture showed hypochromic microcytic red cells with normal haemoglobin (Hb) level. Quantitation of Hb using high performance liquid chromatography (HPLC) and capillary electrophoresis (CE) revealed raised Hb F, normal Hb A2 and Hb A levels. There was also small peak of Hb CS noted in CE. H inclusions was negative. Kleihauer test was positive with heterocellular distribution of Hb F among the red cells. DNA analysis for alpha globin gene mutations showed a single -alpha(-3.7) deletion and Hb CS mutation. These findings were suggestive of compound heterozygosity of Hb CS and a single -alpha(-3.7) deletion with a concomitant heterozygous deltabeta thalassaemia. Co-inheritance of Hb CS and a single -alpha(-3.7) deletion is expected to result at the very least in a clinical phenotype similar to that of two alpha genes deletion. However we demonstrate here a phenotypic modification of alpha thalassemia presumptively as a result of co-inheritance with deltabeta chain abnormality as suggested by the high Hb F level.

Matched MeSH terms: Siblings
Fulltext A family study of HbS in a Malay family by molecular analysis

Hafiza A, Noor HH, Noor FA, Azlin I, Ainoon O

Malays J Pathol, 2010 Dec;32(2):137-41.
PMID: 21329186 MyJurnal

Sickle cell disease (SCD) is an inherited red cell disorder, characterized by the tendency of haemoglobin S or sickle haemoglobin to polymerize and assume a characteristic sickle shape. Molecular analysis has been the mainstay of detection method when confirmation is required. Previously a polymerase chain reaction (PCR)-based restriction enzyme analysis was used for this purpose. A simple bidirectional allele-specific amplification, recently described by Waterfall in 2001 was used to detect the GAG --> GTG mutation on codon 6 of the beta globin gene. Two sets of primers for the mutant and the wild type alleles were used in a single PCR reaction to amplify the regions of interest. The resultant PCR products will produce two fragments at 517 and 267 base pair (bp) respectively. This report highlights the investigations for SCD in the family of a 16-year old girl with recurrent painful crisis affecting the lower limbs whereby the family members are asymptomatic for the disease. Her haemoglobin electrophoresis at an alkaline pH showed dense bands at the HbS and HbF regions, while her father and two sisters had bands at HbS, HbF and HbA. The PCR analysis showed that she was homozygous for the mutation by the presence of only one band at 267 bp fragment, while the father and her sisters were heterozygotes, with the presence of two bands at 267 as well as 517 bp fragments. DNA sequencing of the sample confirmed the mutation. In conclusion, this case report highlighted the simple and cheap yet practical method for molecular confirmation of the presence of HbS gene in subjects with homozygous or heterozygous state of the condition.

Matched MeSH terms: Siblings
Fulltext Biochemical profiling in two siblings with mitochondrial 2-methylacetoacetyl-CoA thiolase deficiency

Ngu LH, Zabedah MY, Shanti B, Teh SH

Malays J Pathol, 2008 Dec;30(2):109-14.
PMID: 19291920 MyJurnal

We report the biochemical profiling in two siblings with mitochondrial 2-methylacetoacetyl-CoA thiolase deficiency. Organic aciduria typical of this rare inborn error metabolism was found when the elder sibling presented with an episode of severe ketoacidosis at 20 months of age, which consisted of excessive excretion of ketones, tiglylglycine, 2-methyl-3-hydroxybutyrate, and 2-methylacetoacetate. Blood acylcarnitiness profile showed elevation of C5OH-carnitine, which represents 2-methyl-3-hydroxybutyrylcarnitine. A similar biochemical profile was identified in the younger sibling during screening although he had only mild clinical symptoms. Both patients reported a favourable outcome on follow-up.

Matched MeSH terms: Siblings
Fulltext Familial antithrombin III deficiency in a Malay patient with massive thrombosis

Wan Ab Rahman WS, Abdullah WZ, Hassan MN, Hussin A, Zulkafli Z, Haron J

Malays J Pathol, 2017 Aug;39(2):197-200.
PMID: 28866705 MyJurnal

Patients with low antithrombin III (AT III) has increased risk for arteriovenous thromboembolic (TE) disease. We report a 28-year-old Malay lady who presented with spontaneous right calf pain and swelling of one week duration. She was on oral contraceptive pills and had a history of travelling for a long distance prior to the presentation. Her brother who was diagnosed with AT III deficiency had arterial thrombosis at a young age. She was diagnosed as having right popliteal vein thrombosis by ultrasound and treated with subcutaneous fondaparinux. While on treatment, she developed massive bilateral pulmonary embolism (PE). Thrombophilia study showed reduced AT III activity (38μl/dl) and normal results for protein C, protein S, activated protein C resistance and lupus anticoagulant assays. This patient has heterozygous AT III deficiency added with significant acquired factors responsible for the TE events. Those with AT III deficiency may have resistance to heparin therapy and require higher doses of heparin.

Matched MeSH terms: Siblings
Fulltext Learning styles among year 1 semester 1nursing students in college of nursing Kubang Kerian, Kelantan

Rusnani Ab Latif, Fairani Yusof, Tan, Yok Mui, Nor Suraizai Ibrahim

The Malaysian Journal of Nursing, 2019;10(4):3-11.
MyJurnal

Introduction: Students learn in many ways. Some students are visual learners, while others are auditory or kinesthetic learners. The purpose of the study is to identify the learning style of the students and factors that influence their learning styles. Methods: This is a descriptive study with cross-sectional design. Convenient sampling was used. In this study, a total of 51 nursing students were involved. A set of questionnaires using VARK (Visual; Auditory; Read/Write; Kinesthetic) inventory was used. Descriptive statistics and Chi-square test were use. Results: The learning styles of the respondents were mostly kinesthetic learning style and auditory learning styles which is 14(27.5%) for both, ten respondent had combinations of various styles, seven respondents had read write learning style and six respondent had visual learning style which is 13.7% and 11.8% respectively. Chi-square test shows that there was significant difference between learning style and respondents' demographic factors of previous school and number of siblings, where p-value 0.05). Conclusion: In order to achieve the goal of student learning it is important to use a combination of teaching methods and to make the classroom environment as stimulating and interactive as possible

Matched MeSH terms: Siblings
Newborn Screening TSH Values Less Than 15 mIU/L Are Not Associated With Long-term Hypothyroidism or Cognitive Impairment

West R, Hong J, Derraik JGB, Webster D, Heather NL, Hofman PL

J Clin Endocrinol Metab, 2020 09 01;105(9).
PMID: 32598474 DOI: 10.1210/clinem/dgaa415

BACKGROUND: It is unclear whether newborns with mild thyrotropin elevation (mTSHe) are at risk of neurocognitive impairment. We assessed whether mTSHe at birth persists during childhood and compared neurocognitive functioning to siblings.
METHODS: This study encompassed children born in the Auckland region (New Zealand) with a newborn screen TSH level of 8 to 14 mIU/L blood, age 6.9 to 12.6 years at assessment, and their siblings. Thyroid function tests (serum TSH and free thyroxine) and neurocognitive assessments were performed, including IQ via the Wechsler Intelligence Scale for Children, fourth edition.
RESULTS: Ninety-six mTSHe individuals were studied, including 67 children recruited with 75 sibling controls. Mean mTSHe newborn TSH level was 10.1 mIU/L blood and 2.4 mIU/L at assessment (range, 0.8-7.0 mIU/L, serum). Although higher newborn TSH levels in the mTSHe group correlated with lower full-scale IQ scores (r = 0.25; P = .040), they were not associated with the magnitude of the IQ difference within sibling pairs (P = .56). Cognitive scores were similar for mTSHe and controls (full-scale IQ 107 vs 109; P = .36), with a minor isolated difference in motor coordination scores.
CONCLUSIONS: Our data do not suggest long-term negative effects of neonatal mild TSH elevation. TSH elevation below the screen threshold appears largely transient, and midchildhood neurocognitive performance of these children was similar to their siblings. We propose that associations between neonatal mild TSH elevation and IQ are due to familial confounders. We caution against the practice of reducing screening CH cutoffs to levels at which the diagnosis may not offer long-term benefit for those detected.

Matched MeSH terms: Siblings
Malaysian siblings with friedreich ataxia and chorea: a novel deletion in the frataxin gene

Spacey SD, Szczygielski BI, Young SP, Hukin J, Selby K, Snutch TP

Can J Neurol Sci, 2004 Aug;31(3):383-6.
PMID: 15376485

BACKGROUND: Friedrich ataxia (FRDA1) is most often the result of a homozygous GAA repeat expansion in the first intron of the frataxin gene (FRDA gene). This condition is seen in individuals of European, North African, Middle Eastern and Indian descent and has not been reported in Southeast Asian populations. Approximately 4% of FRDA1 patients are compound heterozygotes. These patients have a GAA expansion on one allele and a point mutation on the other and have been reported to have an atypical phenotype.
OBJECTIVE: To describe a novel dinucleotide deletion in the FRDA gene in two Malaysian siblings with FRDA1.
SETTING: Tertiary referral university hospital setting.
PATIENTS AND METHODS: A previously healthy 10-year-old Malaysian boy, presented with fever, lethargy, headaches, dysarthria, dysphagia, vertigo and ataxia which developed over a one week period. His neurological exam revealed evidence of dysarthria and ataxia, mild generalized weakness and choreoform movements of the tongue and hands. His reflexes were absent and Babinski sign was present bilaterally. A nine-year-old sister was found to have mild ataxia but was otherwise neurologically intact.
RESULTS: Molecular genetic studies demonstrated that both siblings were compound heterozygotes with a GAA expansion on one allele and a novel dinucleotide deletion on the other allele.
CONCLUSIONS: We describe a novel dinucleotide deletion in the first exon of the FRDA gene in two siblings with FRDA1. Additionally this is the first report of FRDA1 occurring in a family of southeast Asian descent, it demonstrates intrafamilial phenotypic variability, and confirms that atypical phenotypes are associated with compound heterozygosity.

Matched MeSH terms: Siblings
Risk of Colorectal Neoplasia in Individuals With Self-Reported Family History: A Prospective Colonoscopy Study from 16 Asia-Pacific Regions

Wong MC, Ching JY, Chiu HM, Wu KC, Rerknimitr R, Li J, et al.

Am J Gastroenterol, 2016 11;111(11):1621-1629.
PMID: 26977757 DOI: 10.1038/ajg.2016.52

OBJECTIVES: We tested the hypothesis that the risk of colorectal cancer (CRC), advanced colorectal neoplasia (ACN), and colorectal adenoma among screening participants with different first-degree relatives (FDRs) affected by CRC was similar.
METHODS: A multi-center, prospective colonoscopy study involving 16 Asia-Pacific regions was performed from 2008 to 2015. Consecutive self-referred CRC screening participants aged 40-70 years were recruited, and each subject received one direct optical colonoscopy. The prevalence of CRC, ACN, and colorectal adenoma was compared among subjects with different FDRs affected using Pearson's χ2 tests. Binary logistic regression analyses were performed to evaluate the risk of these lesions, controlling for recognized risk factors including age, gender, smoking habits, alcohol drinking, body mass index, and the presence of diabetes mellitus.
RESULTS: Among 11,797 asymptomatic subjects, the prevalence of CRC was 0.6% (none: 0.6%; siblings: 1.1%; mother: 0.5%; father: 1.2%; ≥2 members: 3.1%, P<0.001), that of ACN was 6.5% (none: 6.1%; siblings: 8.3%; mother: 7.7%; father: 8.7%; ≥2 members: 9.3%, P<0.001), and that of colorectal adenoma was 29.3% (none: 28.6%; siblings: 33.5%; mother: 31.8%; father: 31.1%; ≥2 members: 38.1%, P<0.001). In multivariate regression analyses, subjects with at least one FDR affected were significantly more likely to have CRC (adjusted odds ratio (AOR)=2.02-7.89), ACN (AOR=1.55-2.06), and colorectal adenoma (AOR=1.31-1.92) than those without a family history. The risk of CRC (AOR=0.90, 95% confidence interval (CI) 0.34-2.35, P=0.830), ACN (AOR=1.07, 95% CI 0.75-1.52, P=0.714), and colorectal adenoma (AOR=0.96, 95% CI 0.78-1.19, P=0.718) in subjects with either parent affected was similar to that of subjects with their siblings affected.
CONCLUSIONS: The risk of colorectal neoplasia was similar among subjects with different FDRs affected. These findings do not support the need to discriminate proband identity in screening participants with affected FDRs when their risks of colorectal neoplasia were estimated.

Matched MeSH terms: Siblings*
Fulltext Neonatal intrahepatic cholestasis caused by citrin deficiency in two Malaysian siblings: outcome at one year of life

Thong MK, Boey CC, Sheng JS, Ushikai M, Kobayashi K

Singapore Med J, 2010 Jan;51(1):e12-4.
PMID: 20200759

We report two Malaysian siblings with neonatal intrahepatic cholestasis caused by citrin deficiency (NICCD). The younger sibling, a six-month-old Chinese girl, presented with prolonged neonatal jaundice, and was investigated for biliary atresia. Urine metabolic screen showed the presence of urinary-reducing sugars, and she was treated with a lactose-free formula. NICCD was suspected based on the clinical history, examination and presence of urinary citrulline. Mutation study of the SLC25A13 gene showed the compound heterozygotes, 851del4 and IVS16ins3kb, which confirmed the diagnosis of NICCD in the patient and her three-year-old female sibling, who also had unexplained neonatal cholestasis. Long-term dietary advice, medical surveillance and genetic counselling were provided to the family. The diagnosis of NICCD should be considered in infants with unexplained prolonged jaundice. DNA-based genetic testing of the SLC25A13 gene may be performed to confirm the diagnosis retrospectively. An awareness of this condition may help in early diagnosis using appropriate metabolic and biochemical investigations, thus avoiding invasive investigations in infants with neonatal cholestasis caused by NICCD.

Matched MeSH terms: Siblings
Mating calls description of five species of frogs from the genus Hylarana tschudi 1838 (amphibia, anura, ranidae) from Sarawak, Malaysia

Ramlah Zainudin, Mustafa A. Rahman, Badrul Munir M. Zain, Shukor MN, Norhayati A, Inger RF

Sains Malaysiana, 2010;39.

Recordings of frog calls from the genus Hylarana were conducted at seven study sites in Sarawak, Malaysia. The results showed that each species differs in terms of call characteristics, in which a high number of pulsed note belongs to H. baramica, while high repetition note belongs to the sibling species, H. glandulosa. Higher pitched and number of amplitude spectrum, however, belong to H. signata. Pulsed note and note repetition differed significantly among species, except for spectrum amplitude. Advertisement calls for each species were described in detail. This study provide a baseline data on advertisement call characteristics of frogs from the genus Hylarana for future studies of these frogs particularly and the Oriental frogs generally.

Matched MeSH terms: Siblings
Familial neuromyelitis optica spectrum disorder in a pair of sisters

Cheo SW, Ong SAM, Low QJ, Tan YA, Chia YK

QJM, 2020 Oct 01;113(10):743-746.
PMID: 32240316 DOI: 10.1093/qjmed/hcaa107
Matched MeSH terms: Siblings
Altered body composition, sarcopenia, frailty, and their clinico-biological correlates, in Parkinson's disease

Tan AH, Hew YC, Lim SY, Ramli NM, Kamaruzzaman SB, Tan MP, et al.

Parkinsonism Relat Disord, 2018 11;56:58-64.
PMID: 29914840 DOI: 10.1016/j.parkreldis.2018.06.020

INTRODUCTION: Low body weight in Parkinson's disease (PD) is poorly understood despite the associated risks of malnutrition, fractures, and death. Sarcopenia (loss of muscle bulk and strength) and frailty are geriatric syndromes that are likewise associated with adverse health outcomes, yet have received scant attention in PD. We studied body composition, sarcopenia, frailty, and their clinico-biological correlates in PD.
METHODS: 93 patients and 78 spousal/sibling controls underwent comprehensive assessment of diet, clinical status, muscle strength/performance, frailty, body composition (using dual-energy X-ray absorptiometry), and serum levels of neurogastrointestinal hormones and inflammatory markers.
RESULTS: PD patients were older than controls (66.0 ± 8.5 vs. 62.4 ± 8.4years, P = 0.003). Mean body mass index (24.0 ± 0.4 vs. 25.6 ± 0.5kg/m2, Padjusted = 0.016), fat mass index (7.4 ± 0.3 vs. 9.0 ± 0.3kg/m2, Padjusted<0.001), and whole-body fat percentage (30.7 ± 0.8 vs. 35.7 ± 0.9%, Padjusted<0.001) were lower in patients, even after controlling for age and gender. There were no between-group differences in skeletal muscle mass index and whole-body bone mineral density. Body composition parameters did not correlate with disease duration or motor severity. Reduced whole-body fat percentage was associated with higher risk of motor response complications as well as higher levels of insulin-growth factor-1 and inflammatory markers. PD patients had a higher prevalence of sarcopenia (17.2% vs. 10.3%, Padjusted = 0.340) and frailty (69.4% vs. 24.2%, Padjusted = 0.010). Older age and worse PD motor severity were predictors of frailty in PD.
CONCLUSIONS: We found reduced body fat with relatively preserved skeletal muscle mass, and a high prevalence of frailty, in PD. Further studies are needed to understand the patho-mechanisms underlying these alterations.

Matched MeSH terms: Siblings
Bone loss with antiepileptic drug therapy: a twin and sibling study

Shiek Ahmad B, Petty SJ, Gorelik A, O'Brien TJ, Hill KD, Christie JJ, et al.

Osteoporos Int, 2017 Sep;28(9):2591-2600.
PMID: 28589417 DOI: 10.1007/s00198-017-4098-9

Changes in areal bone mineral density (aBMD) and other predictors of bone loss were evaluated in 48 same-sex twin/age-matched sibling pairs discordant for antiepileptic drug (AED) use. AED users had reduced BMD at the hip regions. Prolonged AED users had greater aBMD loss, predicting a higher risk of bone fragility.
INTRODUCTION: To investigate the longitudinal associations of bone mineral measures with antiepileptic drug (AED) use, including enzyme-inducing (EIAED) and non-enzyme-inducing (NEIAED) types, and other predictors of bone loss in a study of 48 same-sex twin/age-matched sibling pairs (40 female, 8 male) discordant for AED use.
METHODS: Using dual-energy X-ray absorptiometry (DXA), areal bone mineral density (aBMD) and content (BMC) at the hip regions, forearm, lumbar spine, and whole body were measured twice, at least 2 years apart. The mean within-pair difference (MWPD), MWPD%, and mean annual rate of aBMD change were adjusted for age, weight, and height. Predictors of bone loss were evaluated.
RESULTS: AED users, compared to non-users, at baseline and follow-up, respectively, had reduced aBMD at the total hip (MWPD% 3.8, 4.4%), femoral neck (4.7, 4.5%), and trochanter regions (4.1, 4.6%) (p 0.05) regions did not differ within pairs. Nevertheless, EIAED users had greater aBMD loss than non-users (n = 20 pairs) at the total hip (1.7 vs. 0.3%, p = 0.013) and whole body regions (0.7% loss vs. 0.1% BMD gain, p = 0.019), which was not found in NEIAED-discordant pairs (n = 16). AED use >20 years predicted higher aBMD loss at the forearm (p = 0.028), whole body (p = 0.010), and whole body BMC (p = 0.031).
CONCLUSIONS: AED users had reduced aBMD at the hip regions. Prolonged users and EIAED users had greater aBMD loss, predicting a higher risk of bone fragility. Further prospective studies of AED effects on bone microarchitecture are needed.

Matched MeSH terms: Siblings
Fulltext Identification of two novel mutations, PSEN1 E280K and PRNP G127S, in a Malaysian family

Ch'ng GS, An SS, Bae SO, Bagyinszky E, Kim S

Neuropsychiatr Dis Treat, 2015;11:2315-22.
PMID: 26396515 DOI: 10.2147/NDT.S86334

Alzheimer's disease (AD) is the most common form of dementia, which can be categorized into two main forms: early onset AD and late onset AD. The genetic background of early onset AD is well understood, and three genes, the APP, PSEN1, and PSEN2 have been identified as causative genes. In the current study, we tested three siblings from Malaysia who were diagnosed with early onset dementia, as well as their available family members. The family history was positive as their deceased father was similarly affected. Patients were tested for mutations in APP, PSEN1, PSEN2, and PRNP. A novel variant, E280K, was discovered in exon 8 of PSEN1 in the three siblings. In silico analyses with SIFT, SNAP, and PolyPhen2 prediction tools and three-dimensional modeling were performed, and the results suggested that the mutation is probably a pathogenic variant. Two additional pathogenic mutations were previously been described for codon 280, E280A, and E280G, which could support the importance of the E280 residue in the PS1 protein contributing to the pathogenic nature of E280K. Additional ten family members were screened for the E280K mutation, and all of them were negative. Six of them presented with a variety of neuropsychiatric symptoms, including learning disabilities, epilepsy, and schizophrenia, while four family members were asymptomatic. A novel PRNP G127S mutation was found in a step-niece of the three siblings harboring the PSEN1 E280K mutation. In silico predictions for PRNP G127S mutation suggested that this might be possibly a damaging variant. Additional studies to characterize PRNP G127S would be necessary to further understand the effects of this mutation.

Matched MeSH terms: Siblings

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