Paracentric inversion of chromosome 18 is a rare cytogenetic abnormality. The vast majority of paracentric inversions are harmless and the offspring of paracentric inversion carriers have only slightly elevated risks for unbalanced karyotypes. However, various clinical phenotypes are seen due to breakpoint variation or recombination. We report a prenatally detected case of familial paracentric inversion of chromosome 18, inv(18)(q21.1q22), with normal clinical features.
Chromosome Aberrations ; Chromosomes, Human, Pair 18 ; Karyotype ; Phenotype ; Recombination, Genetic

Holt-Oram syndrome (HOS) is the most common heart-hand syndrome, which is inherited in an autosomal dominant manner, but most cases are sporadic. This condition is characterized by upper-extremity malformations involving radial-ray, thenar, and carpal bones, and congenital heart malformations including atrial septal defect and ventricular septal defect. It is caused by mutations in the TBX5 gene. In this report, a Korean case with HOS is described, which is inherited from her father. A novel nonsense mutation, p.Glu294*, was identified. This is the first Korean case with HOS confirmed by genetic testing.
Abnormalities, Multiple ; Carpal Bones ; Codon, Nonsense ; Fathers ; Genetic Testing ; Heart ; Heart Defects, Congenital ; Heart Septal Defects, Atrial ; Heart Septal Defects, Ventricular ; Humans ; Lower Extremity Deformities, Congenital ; Upper Extremity Deformities, Congenital

Paracentric inversion of chromosome 18 is a rare cytogenetic abnormality. The vast majority of paracentric inversions are harmless and the offspring of paracentric inversion carriers have only slightly elevated risks for unbalanced karyotypes. However, various clinical phenotypes are seen due to breakpoint variation or recombination. We report a prenatally detected case of familial paracentric inversion of chromosome 18, inv(18)(q21.1q22), with normal clinical features.
Chromosome Aberrations ; Chromosomes, Human, Pair 18 ; Karyotype ; Phenotype ; Recombination, Genetic

Kniest syndrome (OMIM #156550) is a rare autosomal dominant disorder caused by a dysfunction of type II collagen, which is encoded by the COL2A1 gene (OMIM +120140) mapped to chromosome 12q13.11. Type II collagen, a molecule found mostly in the cartilage and vitreous tissues, is essential for the normal development of bones and other connective tissues. Kniest syndrome is a type II collagenopathy that presents as skeletal abnormality associated with disproportionate dwarfism, kyphoscoliosis, enlarged joints, visual loss, hearing loss, and cleft palate. This report describes a Korean patient with Kniest syndrome who was diagnosed with typical clinical features and radiologic findings. The patient presented with disproportionately short stature and kyphoscoliosis from birth. A skeletal survey revealed fused lamina in the thoracic spine, hemivertebrae, flexion deformities in multiple joints, and plagiocephaly.
Cartilage ; Cleft Palate ; Collagen Type II ; Congenital Abnormalities ; Connective Tissue ; Dwarfism ; Hearing Loss ; Humans ; Joints ; Parturition ; Plagiocephaly ; Spine

Holt-Oram syndrome (HOS) is the most common heart-hand syndrome, which is inherited in an autosomal dominant manner, but most cases are sporadic. This condition is characterized by upper-extremity malformations involving radial-ray, thenar, and carpal bones, and congenital heart malformations including atrial septal defect and ventricular septal defect. It is caused by mutations in the TBX5 gene. In this report, a Korean case with HOS is described, which is inherited from her father. A novel nonsense mutation, p.Glu294*, was identified. This is the first Korean case with HOS confirmed by genetic testing.
Abnormalities, Multiple ; Carpal Bones ; Codon, Nonsense ; Fathers ; Genetic Testing ; Heart ; Heart Defects, Congenital ; Heart Septal Defects, Atrial ; Heart Septal Defects, Ventricular ; Humans ; Lower Extremity Deformities, Congenital ; Upper Extremity Deformities, Congenital

Campomelic dysplasia (CMD) is a rare, often lethal, genetic disorder characterized by multiple congenital anomalies and abnormal development of the reproductive organs in males. Mutations in the SOX9 gene are known to cause CMD. We present a Korean CMD girl with a normal 46,XX karyotype and a female reproductive organ phenotype. She was born at 2.35 kg at 38 weeks of gestation and showed characteristic phenotypes, including cleft palate, micrognathia, hypertelorism, flat nasal bridge, congenital bowing of limbs, hypoplastic scapulae, deformed pelvis, and 11 pairs of ribs. She also had an atrioseptal defect of the heart and marked laryngotracheomalacia requiring tracheostomy and tracheopexy. SOX9 mutation analysis revealed the presence of a novel nonsense mutation, p.Gln369*, and the patient was genetically confirmed to have CMD. Although she showed marked failure to thrive and neurodevelopmental delay, she is now 40 months of age and is the only surviving patient with CMD in Korea.
Campomelic Dysplasia ; Cleft Palate ; Codon, Nonsense ; Extremities ; Failure to Thrive ; Female ; Heart ; Humans ; Hypertelorism ; Karyotype ; Korea ; Male ; Pelvis ; Phenotype ; Pregnancy ; Ribs ; Scapula ; Tracheostomy

Kniest syndrome (OMIM #156550) is a rare autosomal dominant disorder caused by a dysfunction of type II collagen, which is encoded by the COL2A1 gene (OMIM +120140) mapped to chromosome 12q13.11. Type II collagen, a molecule found mostly in the cartilage and vitreous tissues, is essential for the normal development of bones and other connective tissues. Kniest syndrome is a type II collagenopathy that presents as skeletal abnormality associated with disproportionate dwarfism, kyphoscoliosis, enlarged joints, visual loss, hearing loss, and cleft palate. This report describes a Korean patient with Kniest syndrome who was diagnosed with typical clinical features and radiologic findings. The patient presented with disproportionately short stature and kyphoscoliosis from birth. A skeletal survey revealed fused lamina in the thoracic spine, hemivertebrae, flexion deformities in multiple joints, and plagiocephaly.
Cartilage ; Cleft Palate ; Collagen Type II ; Congenital Abnormalities ; Connective Tissue ; Dwarfism ; Hearing Loss ; Humans ; Joints ; Parturition ; Plagiocephaly ; Spine

PURPOSE: Neurofibromatosis type 1 (NF1), which is caused by mutations of the NF1 gene, is the most frequent single gene disorder to affect the nervous system. Unidentified bright objects (UBOs) are commonly observed on brain magnetic resonance imaging (MRI) in patients with NF1. However, their clinical and pathologic significance is not well understood. The purpose of this study was to investigate the correlation between UBOs and cerebral glucose metabolism measured by 18F-2-Fluoro-2-deoxy-D-glucose (18F-FDG) positron emission tomography (PET) in Korean patients with NF1. MATERIALS AND METHODS: Medical records of 75 patients (34 males and 41 females) with NF1 who underwent brain MRI and PET between 2005 and 2011 were evaluated retrospectively. Clinical data including demographics, neurological symptoms, and brain MRI and PET findings, were reviewed. RESULTS: UBOs were detected in the brain MRI scans of 31 patients (41%). The region most frequently affected by UBOs was the basal ganglia. The most frequent brain PET finding was thalamic glucose hypometabolism (45/75, 60%). Of the 31 patients with UBOs, 26 had thalamic glucose hypometabolism on brain PET, but the other 5 had normal brain PET findings. Conversely, of the 45 patients with thalamic glucose hypometabolism on brain PET, 26 showed UBOs on their brain MRI scans, but 19 had normal findings on brain MRI scans. CONCLUSION: UBOs on brain MRI scans and thalamic glucose hypometabolism on PET appear to be 2 distinctive features of NF1 rather than correlated symptoms. Because the clinical significance of these abnormal imaging findings remains unclear, a longitudinal follow-up study of changes in clinical manifestations and imaging findings is necessary.
Basal Ganglia ; Brain ; Demography ; Follow-Up Studies ; Genes, Neurofibromatosis 1 ; Glucose ; Humans ; Magnetic Resonance Imaging ; Magnetic Resonance Spectroscopy ; Magnetics ; Magnets ; Male ; Medical Records ; Nervous System ; Neurofibromatoses ; Neurofibromatosis 1 ; Positron-Emission Tomography ; Retrospective Studies

Campomelic dysplasia (CMD) is a rare, often lethal, genetic disorder characterized by multiple congenital anomalies and abnormal development of the reproductive organs in males. Mutations in the SOX9 gene are known to cause CMD. We present a Korean CMD girl with a normal 46,XX karyotype and a female reproductive organ phenotype. She was born at 2.35 kg at 38 weeks of gestation and showed characteristic phenotypes, including cleft palate, micrognathia, hypertelorism, flat nasal bridge, congenital bowing of limbs, hypoplastic scapulae, deformed pelvis, and 11 pairs of ribs. She also had an atrioseptal defect of the heart and marked laryngotracheomalacia requiring tracheostomy and tracheopexy. SOX9 mutation analysis revealed the presence of a novel nonsense mutation, p.Gln369*, and the patient was genetically confirmed to have CMD. Although she showed marked failure to thrive and neurodevelopmental delay, she is now 40 months of age and is the only surviving patient with CMD in Korea.
Campomelic Dysplasia ; Cleft Palate ; Codon, Nonsense ; Extremities ; Failure to Thrive ; Female ; Heart ; Humans ; Hypertelorism ; Karyotype ; Korea ; Male ; Pelvis ; Phenotype ; Pregnancy ; Ribs ; Scapula ; Tracheostomy

PURPOSE: The aim of this nested case-control study was to investigate the association between hepatocyte growth factor (HGF) concentrations in maternal plasma and the risk of developing preeclampsia. MATERIALS AND METHODS: Plasma HGF concentration were measured in 52 women who subsequently developed preeclampsia and 104 normal pregnant women at the time of genetic amniocentesis (15-20 weeks) by enzyme-linked immunosorbent assay. RESULTS: Maternal plasma HGF concentrations were significantly higher in women with subsequent preeclampsia (median: 737.8 ng/mL vs. 670.4 ng/mL, P=0.003) than in normal controls. However, HGF concentrations were not significantly different between subgroups by preeclamptic complications. After adjusting for potential confounding factors, women with HGF concentrations > or =702.5 ng/mL had a 3.2-fold increased risk (95% CI 2.7-5.4, P<0.001) of subsequent development of preeclampsia compared with women with HGF concentrations <702.5 ng/mL. CONCLUSION: Elevated maternal plasma HGF concentrations in the early second-trimester are associated with an increased risk of developing preeclampsia.
Amniocentesis ; Case-Control Studies ; Female ; Hepatocyte Growth Factor ; Hepatocytes ; Humans ; Plasma ; Pre-Eclampsia ; Pregnant Women ; Risk Factors