Adenosine ; Diagnosis ; Humans ; Ichthyosis ; Ichthyosis, Lamellar ; Infant, Newborn ; Pregnancy ; Prenatal Diagnosis ; Skin ; Ultrasonography ; Wills

The nineteenth century neuroscience studied the instinct of animal to understand the human mind. In particular, it has been found that the inheritance of unconscious behavior like instinct is mediated through ganglion chains, such as the spinal cord or sympathetic nervous system, which control unconscious reflexes. At the same time, the theory of Inheritance of Acquired Characteristics (hereafter ‘IAC’) widely known as Lamarck's evolutionary theory provided the theoretical frame on the origin of instinct and the heredity of action that the parental generation's habits were converted into the nature of the offspring generation. Contrary to conventional knowledge, this theory was not originally invented by Lamarck, and Darwin also did not discard this theory even after discovering the theory of natural selection in 1838 and maintained it throughout his intellectual life. Above all, in the field of epigenetics, the theory of ‘IAC’ has gained attention as a reliable scientific theory today. Darwin discovered crucial errors in the late 1830s that the Lamarck version's theory of ‘IAC’ did not adequately account for the principle of the inheritance of unconscious behavior like instinct. Lamarck's theory regarded habits as conscious and willful acts and saw that those habits are transmitted through the brain to control conscious actions. Lamarck's theory could not account for the complex and elaborate instincts of invertebrate animals, such as brainless ants. Contrary to Lamarck's view, Darwin established the new theory of ‘IAC’ that could be combined with contemporary neurological theory, which explains the heredity of unconscious behavior. Based on the knowledge of neurology, Darwin was able to translate the ‘principle of habit’ into a neurological term called ‘principle of reflex’. This article focuses on how Darwin join the theory of ‘IAC’ with nineteenth century neuroscience and how the neurological knowledge from the nineteenth century contributed to Darwin's overcoming of Lamarck's ‘IAC’. The significance of this study is to elucidate Darwin's notion of ‘IAC’ theory rather than natural selection theory as a principle of heredity of behavior. The theory of ‘IAC’ was able to account for the rapid variation of instincts in a relatively short period of time, unlike natural selection, which operates slowly in geological time spans of tens of millions of years. The nineteenth century neurological theory also provided neurological principles for ‘plasticity of instinct,’ empirically supporting the fact that all nervous systems responsible for reflexes respond sensitively to very fine stimuli. However, researchers of neo-Darwinian tendencies, such as Richard Dawkins and evolutionary psychologists advocating the ‘selfish gene’ hypothesis, which today claim to be Darwin's descendants, are characterized by human nature embedded in biological information, such as the brain and genes, so that it cannot change at all. This study aims to contribute to reconstructing the evolutionary discourse by illuminating Darwin's insights into the “plasticity of nature” that instincts can change relatively easily even at the level of invertebrates such as earthworms.
Animals ; Ants ; Brain ; Epigenomics ; Ganglion Cysts ; Heredity ; Human Characteristics ; Humans ; Instinct ; Invertebrates ; Nervous System ; Neurology ; Neurosciences ; Oligochaeta ; Parents ; Psychology ; Reflex ; Selection, Genetic ; Spinal Cord ; Sympathetic Nervous System ; Transcutaneous Electric Nerve Stimulation ; Wills

PURPOSE: This study sought to understand and describe the pregnancy and childbirth experiences of women with epilepsy (WWE). METHODS: Datawere collected from 2016e2017 through in-depth individual interviews with 12 WWE who experienced childbirth within 36 months. Verbatim transcripts were analyzed following Colaizzi's phenomenological analysis to uncover the meaning of the experiences of the participants. RESULTS: The pregnancy and childbirth experiences of WWE were clustered into four theme clusters and 8 themes from20 meaning units: 1) Feeling anxious due to unplanned pregnancy and unexpected changes; 2) Standing at crossroads that never guarantee satisfaction; 3) Carrying a burden of fearful expectation and daily routines; 4) Enjoying rewards of pregnancy and childbirth as a woman with epilepsy. CONCLUSION: WWE had strong anxiety about the possible abnormality of their babies during pregnancy. They had mixed feelings about delivery and had to make a tough decision about breastfeeding because of antiepileptic drugs use. After childbirth, they had increased fear about the possible inheritance of the illness and had a hard time managing the burden of childcare and seizure control. However, pregnancy allows these women to gain disease awareness and further appreciate the importance of their health. The study results indicate the need for multidisciplinary intervention for WWE, before, during, and after pregnancy to increase communication with health professionals. Especially, preconception counselling and education led by nurses are required.
Anticonvulsants ; Anxiety ; Breast Feeding ; Education ; Epilepsy ; Female ; Health Occupations ; Humans ; Parturition ; Pregnancy ; Pregnancy, Unplanned ; Qualitative Research ; Reward ; Seizures ; Wills

Tatton-Brown-Rahman Syndrome (TBRS), an overgrowth syndrome caused by heterozygous mutation of DNMT3A, first was described in 2014. Approximately 60 DNMT3A variants, including 32 missense variants, have been reported, with most missense mutations located on the DNMT3A functional domains. Autosomal dominant inheritance by germ-line mutation of DNMT3A has been reported, but vertical transmission within a family is extremely rare. Herein, we report the first Korean family with maternally inherited TBRS due to the novel heterozygous DNMT3A variant c.118G>C p.(Glu40Gln), located outside the main functional domain and identified by multigene panel sequencing. The patient and her mother had typical clinical features, including tall stature during childhood, macrocephaly, intellectual disability, and characteristic facial appearance. TBRS shows milder dysmorphic features than other overgrowth syndromes, potentially leading to underdiagnosis and underestimated prevalence; thus, targeted multigene panel sequencing including DNMT3A will be a useful tool in cases of overgrowth and unexplained mild intellectual disability for early diagnosis and genetic counseling.
Early Diagnosis ; Genetic Counseling ; Germ-Line Mutation ; Growth Disorders ; High-Throughput Nucleotide Sequencing ; Humans ; Intellectual Disability ; Megalencephaly ; Mothers ; Mutation, Missense ; Prevalence ; Sequence Analysis, DNA ; Wills

Steatocystoma multiplex is an uncommon benign skin disease, which typically manifests as numerous intradermal cysts that can be scattered anywhere on the body. Although usually asymptomatic, it can be significantly disfiguring. One type of steatocystoma multiplex is known to be associated with the autosomal dominant inheritance of a mutation in the gene coding for keratin 17 (KRT17). In such cases, it is often concurrent with other developmental abnormalities of the ectoderm-derived tissues, such as the nails, hair, and teeth. To the best of our knowledge, few cases have been reported of steatocystoma multiplex of the oral and maxillofacial region. This report describes a case of steatocystoma multiplex of both sides of the neck and multiple dental anomalies, with a focus on its clinical, radiological, and histopathological characteristics, as well as the possibility that the patient exhibited the familial type of this condition.
Clinical Coding ; Hair ; Humans ; Keratin-17 ; Neck ; Skin Diseases ; Steatocystoma Multiplex ; Tooth ; Wills

OBJECTIVES: Psychological stress has been known to increase the risk of schizophrenia. Because stress responses are mainly mediated by cortisol, the action of the glucocorticoid receptors (Nuclear Receptor Subfamily 3 Group C Member 1, NR3C1) is possibly related to the pathogenesis of schizophrenia. In this study, we investigated the associations between polymorphisms of NR3C1 and schizophrenia.METHODS: Four single nucleotide polymorphisms (SNPs) (rs17100236, rs2963155, rs9324924, and rs7701443) of NR3C1 were genotyped in 208 patients with schizophrenia and 339 healthy individuals. A chi-square test was performed to test differences in allele distributions among groups. A multiple logistic regression model was used to calculate odds ratios (ORs) and 95% confidence intervals (CIs), and multiple inheritance models to analyze the associations between schizophrenia and SNPs (the dominant, recessive and additive models).RESULTS: The minor allele frequencies of two SNPs were significantly higher in the schizophrenia group than in those of the control group (rs2963155 G > A : 0.25 vs. 0.18, p = 0.0066 ; rs7701443 A > G : 0.40 vs. 0.33, p = 0.012). The genotype frequencies of two SNPs were found to be significantly different between patients with schizophrenia and controls in the dominant model (rs2963155 : AG/GG vs. AA, OR = 1.66, 95% CI = 1.16–2.38, p = 0.0055, rs7701443 : AG/AA vs. GG, OR = 1.61, 95% CI = 1.11–2.34, p = 0.01) and the log-additive model (rs2963155 : AG vs. GG vs. AA, OR = 1.54, 95% CI = 1.13–2.10, p = 0.0067).CONCLUSIONS: This study showed significant associations between NR3C1 polymorphisms and schizophrenia. It suggests that NR3C1 may play a role in the pathogenesis of schizophrenia.
Alleles ; Gene Frequency ; Genetic Predisposition to Disease ; Genotype ; Humans ; Hydrocortisone ; Logistic Models ; Odds Ratio ; Polymorphism, Genetic ; Polymorphism, Single Nucleotide ; Receptors, Glucocorticoid ; Schizophrenia ; Stress, Psychological ; Wills

BACKGROUND AND OBJECTIVES: To analyse the audiometric profile and the pedigree of a large family with otosclerosis to understand the inheritance pattern and its implication in clinical management of the disease. SUBJECTS AND METHODS: Pedigree analysis was performed on the basis of family history and audiometric tests. Pure tone audiometry, tympanometry, and acoustic reflexes were evaluated for the family members. Audiometric analysis was also carried out for the individuals who have already underwent corrective surgery at the time of study. RESULTS: Out of 112 family members, 17 were affected individuals, and 11 of them were surgically confirmed. Hearing loss (HL) started unilaterally and progressed to bilateral form. Otosclerosis was presented in early 20’s in the first and second generations but it was delayed to mid-late 30’s in the fourth generation. An affected female was diagnosed with otosclerosis during her pregnancy. Though the disease was familial, a mother of four affected offspring in this family did not develop otosclerosis until she died at the age of 84. CONCLUSIONS: The five-generation family, which was analysed in the present study, exhibited autosomal dominant inheritance of otosclerosis with reduced penetrance. Bilateral HL and pregnancy-aggravated otosclerosis were observed in this family. It was found for the first time that the age of onset of the disease delayed in the successive generations. The current study indicated the importance of detailed pedigree analysis for better clinical management of otosclerosis.
Acoustic Impedance Tests ; Age of Onset ; Audiometry ; Family Characteristics ; Female ; Hearing Loss ; Hearing Loss, Conductive ; Humans ; Inheritance Patterns ; Mothers ; Otosclerosis ; Pedigree ; Penetrance ; Pregnancy ; Reflex, Acoustic ; Wills

Primary distal renal tubular acidosis (dRTA) caused by mutations of the SLC4A1 gene, which encodes for erythroid and kidney isoforms of anion exchanger, shows marked difference in inheritance patterns and clinical features in different parts of the world. While the disease shows autosomal dominant inheritance without any red cell morphological abnormalities in the temperate countries, it is almost invariably recessive, and often accompanies red cell morphological abnormalities or hemolytic anemia in the tropics, especially in Southeast Asia. Here, we report three patients with autosomal recessive (AR) dRTA, presenting with typical findings of failure to thrive and rickets, from two unrelated Lao families. The mutational analyses revealed that all three patients harbored the same homozygous SLC4A1 mutation, p.Gly701Asp. Adequate supplementation of alkali and potassium resulted in remarkable improvement of growth retardation and skeletal deformities of the patients. This is the first case report of Lao patients with AR dRTA caused by SLC4A1 mutations.
Acidosis, Renal Tubular* ; Alkalies ; Anemia, Hemolytic ; Asia, Southeastern ; Congenital Abnormalities ; Failure to Thrive ; Humans ; Inheritance Patterns ; Kidney ; Laos ; Potassium ; Protein Isoforms ; Rickets ; Wills

A 1q21.1 microdeletion is an extremely rare chromosomal abnormality that results in phenotypic diversity and incomplete penetrance. Patients with a 1q21.1 microdeletion exhibit neurological-psychiatric problems, microcephaly, epilepsy, facial dysmorphism, cataract, and thrombocytopenia absent radius syndrome. We reported a neonate with confirmed intrauterine growth restriction (IUGR), micrognathia, glossoptosis, upper airway obstruction, facial dysmorphism, and eye abnormality at birth as well as developmental delay at the age of 1 year. These clinical manifestations, except for the IUGR and upper airway obstruction, in the neonate indicated a 1q21.1 microdeletion. Here, we report a rare case of a 1q21.1 microdeletion obtained via paternal inheritance in a newborn with upper airway obstruction caused by glossoptosis and tracheal stenosis.
Airway Obstruction* ; Cataract ; Chromosome Aberrations ; Chromosome Deletion ; Epilepsy ; Eye Abnormalities ; Fetal Growth Retardation ; Glossoptosis ; Humans ; Infant, Newborn* ; Microarray Analysis ; Microcephaly ; Micrognathism ; Parturition ; Penetrance ; Radius ; Thrombocytopenia ; Tracheal Stenosis ; Wills

Limb-girdle muscular dystrophies (LGMD) are heterogeneous disorders with autosomal inheritance. Autosomal dominant LGMD mapped to 7q36.3 has been classified as LGMD type 1D (LGMD1D) in the Human Gene Nomenclature Committee Database. LGMD1D is characterized predominantly by limb-girdle weakness and may also show a bulbar symptom in some cases. In the past, the frequency of this disease was uncommon, and this disorder was mainly found in Europe and the United States. However, recently, this disorder has been reported in Asia, including Japan, Korea, and Taiwan. Here, we report on three LGMD1D patients, including one with a novel mutation in DNAJB6, c.298T>A. While two patients complained of limb-girdle weakness, as would be expected, one patient had distal weakness. They had various serum creatine kinase levels. Radiologic findings in one patient showed fatty degeneration and atrophy in the posterior part of distal muscles. Pathologic findings in one of the patients showed rimmed vacuoles. Although LGMD1D is still uncommon in Korea, we discovered three Korean patients with LGMD1D, including one novel mutation in DNAJB6, p.Phe100Ile (c.298T>A).
Asia ; Atrophy ; Creatine Kinase ; Europe ; Humans ; Japan ; Korea ; Muscles ; Muscular Diseases ; Muscular Dystrophies, Limb-Girdle* ; Taiwan ; United States ; Vacuoles ; Wills