ABSTRACT
TP63 gene mutations have recently been shown to be disease causing in EEC and SHFM. Two other overlapping syndromes with ectrodactyly as a major feature, have been mapped to chromosome 3q27 close by the TP63 locus, namely the LMS and ADULT syndromes. Here, we report on a missense TP63 gene mutation in an isolated ADULT syndrome case. This finding widens the spectrum of abnormalities to be ascribed to TP63 gene in human and emphasise on the variable roles of the different Tp63 isotypes.
Subject(s)
Abnormalities, Multiple/genetics , Genes, Dominant/genetics , Mutation/genetics , Abnormalities, Multiple/diagnosis , Alleles , Child , Female , Genetic Linkage , Genotype , Humans , Limb Deformities, Congenital/diagnosis , Limb Deformities, Congenital/genetics , Nipples/abnormalities , SyndromeABSTRACT
Respiratory chain deficiency (RCD) is responsible for a clinically heterogeneous group of early-onset untreatable disorders. Enzymological prenatal diagnosis (PD) can only be offered to a fraction of families. Moreover, due to the two-fold genetic origin of the respiratory chain (nuclear and mitochondrial DNA) and owing to the large number of nuclear genes involved in the respiratory chain assembly, maintenance and functioning, the identification of the disease causing gene in a given family remains challenging. Here, we report on PD of RCD by direct screening of NDUFV1, SDH-Fp, SCO1 and SURF1 mutations in five unrelated families with complex I, II and IV deficiency, respectively. The identification of the disease-causing gene in a given family with RCD is a major issue to provide both adequate genetic counselling and early, reliable PD.
Subject(s)
Electron Transport/genetics , Fetal Diseases/diagnosis , Genetic Testing , Mitochondrial Myopathies/diagnosis , Prenatal Diagnosis , Electron Transport Complex I , Female , Fetal Diseases/genetics , Humans , Membrane Proteins/genetics , Mitochondria/genetics , Mitochondrial Myopathies/genetics , Mitochondrial Proteins , Molecular Chaperones , Mutation , NADH Dehydrogenase , Predictive Value of Tests , Pregnancy , Proteins/geneticsSubject(s)
Fetus/metabolism , Mutagenesis/genetics , Myotonic Dystrophy/genetics , Prenatal Diagnosis , Protein Serine-Threonine Kinases/genetics , Trinucleotide Repeat Expansion/genetics , Adult , Alleles , Blotting, Southern , DNA Mutational Analysis , Female , Genetic Linkage/genetics , Humans , Male , Microsatellite Repeats/genetics , Middle Aged , Myotonin-Protein Kinase , Pedigree , Polymerase Chain Reaction , PregnancyABSTRACT
The prenatal diagnosis of a 1p36 deletion is reported. The pregnancy was ascertained at 24 weeks of gestation because of the discovery of multiple malformations at ultrasound including hypotelorism, moderate cerebral ventricular dilatation and Ebstein anomaly with secondary cardiac failure. Following cytogenetic studies and counselling, the pregnancy was terminated and a fetal autopsy performed. The phenotype of this antenatally-diagnosed case is compared with the clinical features of 44 previously reported cases with an identical deletion of the short arm of chromosome 1p36.
Subject(s)
Abnormalities, Multiple/genetics , Chromosomes, Human, Pair 1 , Gene Deletion , Prenatal Diagnosis , Adult , Facial Bones/abnormalities , Female , Humans , Hydrops Fetalis/genetics , In Situ Hybridization, Fluorescence , Karyotyping , Male , Pregnancy , Ultrasonography, PrenatalABSTRACT
The prenatal diagnosis of an 8p23.1 deletion is reported. The diagnosis was ascertained at 22 weeks of gestation because of the discovery of a diaphragmatic hernia at ultrasound. Following cytogenetic studies and counselling, the pregnancy was terminated. An autopsy confirmed the presence of a diaphragmatic hernia and revealed also the existence of an atrio-ventricular canal (AVC) and an atrial septal defect (ASD). The clinical features of this antenatally diagnosed case are compared with those observed in 16 previously reported cases with an identical deletion of the short arm of chromosome 8. This suggests that a deletion 8p23.1 should be considered whenever a diaphragmatic hernia and/or an AVC is detected on ultrasound.
Subject(s)
Chromosomes, Human, Pair 8 , Gene Deletion , Hernia, Diaphragmatic/genetics , Prenatal Diagnosis , Adult , Craniofacial Abnormalities/genetics , Female , Hernia, Diaphragmatic/diagnostic imaging , Humans , Pregnancy , Ultrasonography, PrenatalSubject(s)
Gene Deletion , Genetic Counseling , Muscular Atrophy, Spinal/genetics , Cyclic AMP Response Element-Binding Protein , DNA/analysis , Genetic Markers , Humans , Male , Nerve Tissue Proteins/genetics , Nuclear Family , Pedigree , Polymerase Chain Reaction , RNA-Binding Proteins , SMN Complex ProteinsABSTRACT
The survival motor neuron (SMN) gene was lacking in 6/12 patients with arthrogryposis multiplex congenita (AMC) associated with spinal muscular atrophy (SMA). Neither point mutation in the SMN gene nor evidence for linkage to chromosome 5q13 were found in the other patients. Hitherto, arthrogryposis was regarded as an exclusion criterion in SMA. Our data strongly suggest that AMC of neurogenic origin is genetically heterogeneous, with a subgroup being allelic to SMA. Absence or interruption of the SMN gene in the AMC-SMA association will make the diagnosis easier and genetic counselling will now become feasible.
Subject(s)
Arthrogryposis/genetics , Gene Deletion , Nerve Tissue Proteins/genetics , Spinal Muscular Atrophies of Childhood/genetics , Arthrogryposis/complications , Arthrogryposis/etiology , Child , Child, Preschool , Cyclic AMP Response Element-Binding Protein , Dinucleotide Repeats , Female , Humans , Infant , Infant, Newborn , Male , Polymorphism, Genetic , RNA-Binding Proteins , SMN Complex Proteins , Spinal Muscular Atrophies of Childhood/complicationsABSTRACT
Werdnig-Hoffmann disease is a common autosomal recessive neuromuscular disorder that results in paralysis and death. No treatment to prevent this disease or to alter its unremitting course has been found. Recently, linkage analysis with cloned DNA probes has shown that the mutation causing Werdnig-Hoffmann disease is located on chromosome 5q12-q14. We performed genetic analysis for the prenatal diagnosis of Werdnig-Hoffmann disease in seven at risk families. Two fetuses were diagnosed as being affected and the remainder as unaffected, and this was confirmed after birth. This study shows that prenatal diagnosis of Werdnig-Hoffmann disease has become feasible.
