Abstract Genetic disorders are usually considered to be caused by harmful gene mutations, as well as by chromosomal aberrations, including small insertions, duplications and/or deletions. However, as infertile individuals often arise among the offspring of crosses between two fertile mouse strains, we postulate that a certain combination of ‘normal’ genes with neither gene mutations nor chromosomal aberrations can cause such serious phenotypic alterations as reproductive dysfunction. In this study, we show evidence that a combination of multiple normal genes from two different normal mouse strains manifests a wide range of male reproductive dysfunctions, from benign changes to complete infertility. These abnormal phenotypes are thought to have occurred by epistatic interactions of alleles.
Abstract We retrospectively analyzed the reproductive variables and the spontaneous malformations in the historical control data from the embryo-fetal development studies conducted in our laboratories with Kbl:JW rabbits over two decades (1990–2010) and fetal malformations induced by thalidomide in 1988, 1995 and 2007. These analyses in the control animals revealed that the reproductive variables in dams, total frequencies and profile of external, visceral and skeletal abnormalities and/or variations in the fetuses were stable over two decades. In addition, the characteristics of the malformations induced by thalidomide were reproducible at the three time points. Therefore, it is concluded that Kbl:JW rabbit is one of the useful rabbit strains to evaluate the effects of test substances on embryo-fetal development, especially in view of the chronological stability of spontaneous or drug-induced malformations in the fetuses.
ABSTRACT We report a case of osteogenesis imperfecta (OI) (OMIM166210) type II, in which a prenatal diagnosis was made by three-dimensional computed tomography (3D-CT). Subsequent molecular analysis revealed a recurrent, heterozygous mutation in COL1A2. Fetal CT is a powerful tool for visualizing the fetal skeleton and can provide a definitive diagnosis of fetal skeletal dysplasias; however, whether or not its employment for prenatal diagnosis is warranted in terms of fetal radiation risks remains controversial, both medically and ethically. Based on our experience, we review the current state of fetal CT for the diagnosis of skeletal dysplasias, with a discussion of the relevant literature.
ABSTRACT We report a 34-year-old Japanese female with the vascular type of Ehlers-Danlos syndrome. She had thin translucent skin, extensive bruising, toe joint hypermobility, left lower extremity varicose veins, and chronic wrist, knee and ankle joint pain. She also had dizziness caused by autonomic dysfunction. Magnetic resonance angiography showed tortuous vertebral and basilar arteries, mild left carotid canal bulging, and right anterior tibial artery hypoplasia. Electron microscopic examinations of a skin biopsy revealed extremely dilated rough endoplasmic reticulum in dermal fibroblasts and wide variability of individual collagen fibril diameters. A molecular analysis using a conventional total RNA method and a high-resolution melting curve analysis using genomic DNA revealed a novel missense mutation within exon 48 of the COL3A1 gene, c.3428G<A, leading to p.Gly1143Glu.
ABSTRACT The present case report describes two patients with a novel combination of VACTERL (vertebral, anorectal, cardiac, tracheoesophageal, renal, limb), neural tube defect and crossed renal ectopia. Though cases of VACTERL associated with crossed renal ectopia have been described, the present case report is the first to describe its combination with neural tube defect. The cases reported here are significant because central nervous system manifestations are scarce in VACTERL syndrome. The role of sonic hedgehog pathway has been proposed in VACTERL association and neural tube defects. Axial Sonic hedgehog signaling has also been implicated in the mediolateral positioning of the renal parenchyma. With this knowledge, the etiopathogenesis of this novel combination is discussed to highlight the role of sonic hedgehog signaling as a point of coherence.
ABSTRACT Crisponi syndrome is an infrequently described disorder with autosomal recessive trait. It is characterized by extensive muscular contractions in the face after even minimal stimuli or crying, hypertonia, opisthotonus, camptodactyly, and typical facial features. Muscle contractions attenuate during rest or when the infant calms down. As a recently described new disease, Crisponi syndrome may be confused with epileptic manifestations. Most of the patients die in the first months of life due to hyperthermia and feeding problems. Recently, it has been demonstrated that mutations of the CRLF1 gene ‘cytokine receptor-like factor 1’ are associated with Crisponi syndrome. Here, we present a newborn diagnosed with Crisponi syndrome and report a novel homozygous CFRL1 gene mutation.
ABSTRACT A 29-year-old primigravida developed polyhydramnios at 24 weeks of gestation, requiring six serial amnioreductions. In addition, prenatal ultrasound examinations revealed a fetus with small stomach pouch, small thorax, slightly shortened limbs, and skin edema; paternal uniparental disomy 14(upd(14)pat) phenotype was suspected. At 37 weeks, the patient delivered a 2558 g female infant with characteristic facial features, webbed neck, thoracic deformity, abdominal wall defect, skin edema, overlapping fingers, placentomegaly, and small thorax with ‘coat-hanger’ appearance of the ribs on chest X-ray. A phenotype consistent with upd(14)pat was confirmed by DNA analysis. Although the infant's condition was initially stable, hepatoblastoma was subsequently detected and right hepatectomy was performed on day 224. On day 382, the infant was discharged with in-home respiratory management.