ABSTRACT
We herein report a male patient known as having a XYY karyotype. At the age of 26 years a Prader-Willi syndrome (PWS) was diagnosed. Before that time the whole symptomatology was ascribed to the XYY syndrome. This is the first reported association of PWS and polygonosomal abnormality in a male adult (whose height is above average).
Subject(s)
Prader-Willi Syndrome/genetics , Adult , Body Height , Humans , Karyotyping , Male , X Chromosome , Y ChromosomeABSTRACT
Holoprosencephaly (HPE) is a severe brain malformation which results from incomplete cleavage of the forebrain during early embryogenesis. The aetiology of HPE is very heterogeneous. Among the genetic factors, SIX3, which is considered to be the functional orthologue of Drosophila genes sine oculis (so) and optix, has been found to be mutated in the homeodomain, in some patients with HPE (HPE2 on chromosome 2p21). We report a new HPE family, presenting a wide spectrum of clinical features, ranging from cyclopia to hypotelorism, in which a mutation was found for the first time in the SIX domain of SIX3: a GG insertion creates a frameshift leading to a nonsense mutation downstream in the homeodomain region.
Subject(s)
Codon, Nonsense/genetics , Frameshift Mutation/genetics , Genes, Homeobox/genetics , Holoprosencephaly/genetics , Homeodomain Proteins/genetics , Nerve Tissue Proteins/genetics , Chromosomes, Human, Pair 2/genetics , DNA Primers/chemistry , Eye Proteins , Female , Holoprosencephaly/complications , Holoprosencephaly/etiology , Humans , Male , Pedigree , Polymerase Chain Reaction , Polymorphism, Single-Stranded Conformational , Homeobox Protein SIX3ABSTRACT
We report the first case of the association of Sotos syndrome and gastric carcinoma (containing signet ring cells) in a twin patient. The other-probably monozygous-twin is also affected by the Sotos syndrome. The association of malign tumors in Sotos syndrome and other overgrowth syndromes is discussed.
Subject(s)
Brain Diseases/genetics , Carcinoma, Signet Ring Cell/genetics , Gigantism/genetics , Stomach Neoplasms/genetics , Twins, Monozygotic , Adult , HumansABSTRACT
Holoprosencephaly (HPE), the most common developmental defect of the forebrain and the face, is genetically heterogeneous. One of the genes involved, Sonic hedgehog ( SHH ), on 7q36, has been identified as the first HPE-causing gene both in mouse and humans. In order to delineate the phenotype of specific SHH mutations, we described the expression of the SHH gene during early human embryogenesis and investigated the phenotype of novel SHH mutations. In situ hybridization studies were performed on paraffin-embedded human embryo sections at three different development stages. These studies show that SHH is expressed in the notochord, the floorplate, the brain, the zone of polarizing activity and the gut. We also report on the phenotype of four novel mutations identified in 40 HPE families (two in isolated HPE and two in familial HPE). Expressivity ranged from alobar HPE to microcephaly and hypoplasia of the pituitary gland in one family, and from HPE to an asymptomatic form in another family. No SHH mutation was found in six polymalformed cases combining HPE with other defects, such as skeletal, limb, cardiac, anal and/or renal anomalies. This study confirms the genetic heterogeneity of HPE, and further demonstrates that SHH mutations are associated with a broad spectrum of cerebral midline defects.
Subject(s)
Gene Expression Regulation, Developmental/genetics , Holoprosencephaly/genetics , Mutation , Proteins/genetics , Trans-Activators , Brain/embryology , DNA Mutational Analysis , Embryonic and Fetal Development , Female , Hedgehog Proteins , Holoprosencephaly/embryology , Humans , In Situ Hybridization , Male , Pedigree , PhenotypeABSTRACT
We report on a female fetus of 24 weeks whose clinical and radiological findings were compatible with boomerang dysplasia (BD). However, histopathology was unusual with a lateral fan shaped diaphyseal ossification. This has never been described either in typical atelosteogenesis I (AT-I) or in BD. The purpose of this report is to find out if this condition is a separate lethal bone dysplasia or another histological feature of the nosological group of AT-I and BD.
Subject(s)
Osteochondrodysplasias/diagnostic imaging , Bone and Bones/abnormalities , Bone and Bones/diagnostic imaging , Bone and Bones/pathology , Female , Humans , Osteochondrodysplasias/genetics , Osteochondrodysplasias/pathology , RadiographyABSTRACT
Congenital microcoria is an autosomal dominant disorder characterized by a pupil with a diameter <2 mm. It is thought to be due to a maldevelopment of the dilator pupillae muscle of the iris, and it is associated with juvenile-onset glaucoma. A total genome search for the location of the congenital microcoria gene was launched in a single large family. We found linkage between the disease and markers located on 13q31-q32 (Zmax = 9.79; theta = 0). Haplotype analysis narrowed the linked region to an interval <8 cM between markers D13S1239 proximally and D13S1280 distally.
Subject(s)
Chromosomes, Human, Pair 13 , Iris/abnormalities , Chromosome Mapping , Female , Genetic Linkage , Haplotypes , Humans , Male , Pedigree , Recombination, GeneticABSTRACT
Holoprosencephaly (HPE) is a developmental defect due to a failure of cleavage of the forebrain. The brain malformations are usually associated with facial anomalies. From a series of 258 HPE records involving at least one affected child, 97 cases in 79 families with nonsyndromic and nonchromosomal HPE were selected. The male:female ratio was 0.87. A high degree of familial aggregation was observed in 23/79 families (29%). A segregation analysis performed in the 79 nuclear families led to the conclusion that the transmission of nonsyndromic HPE is compatible with an autosomal dominant mode of inheritance. Under this hypothesis, the penetrance was estimated as 82% for major types (alobar, semilobar, lobar) and 88% when major and minor types (atypical) were included. The proportion of sporadic cases was estimated to be 68%. This genetic model allows a prediction of the recurrence risk after an isolated case of 13% for major types and 14% when minor types are included.
Subject(s)
Diseases in Twins/genetics , Holoprosencephaly/genetics , Models, Genetic , Female , Genes, Dominant/genetics , Heterozygote , Humans , Male , Paternal Age , Pedigree , Penetrance , Sex Factors , Twins, Dizygotic , Twins, MonozygoticABSTRACT
Intracerebral cysts and porencephaly or arachnoid cysts are rarely but are repeatedly reported in orofaciodigital (OFD) syndrome type 1. We report on 2 families in which OFD syndrome type 1 was observed with central nervous system (CNS) malformations and 3 sporadic cases of OFD with CNS defects, most likely representing fresh mutations for OFD 1. In one case, vermis hypoplasia was present; in another, periventricular heterotopiae were noted. We review the literature on CNS anomalies in OFD syndromes and stress the difficulties in genetic counseling and functional prognosis for children of OFD 1 female carriers prenatally diagnosed with a malformation of the brain. As for CNS malformations, renal cystic disease is an often overlooked complication specific to OFD 1. In 1 family, cystic medullary disease was noted in OFD 1 carriers, leading 1 patient to dialysis by age 35 years and the other to severe renal insufficiency by age 28 years. Longitudinal follow-up of OFD 1 carriers should be performed, and renal function should be assessed in those with cysts because the functional prognosis of this developmental anomaly may be worse than usually reported in the literature.
Subject(s)
Central Nervous System Diseases/genetics , Kidney Failure, Chronic/genetics , Orofaciodigital Syndromes/complications , Central Nervous System Diseases/complications , Female , Genes, Dominant/genetics , Genetic Counseling , Humans , Kidney Failure, Chronic/complications , Magnetic Resonance Imaging , Orofaciodigital Syndromes/diagnostic imaging , Orofaciodigital Syndromes/genetics , Prognosis , UltrasonographyABSTRACT
We report a family with incontinentia pigmenti. One affected woman had seven pregnancies, seven miscarriages; a prenatal diagnosis by molecular biology was undertaken in the last four cases (two males, two females). In the last two males, a miscarriage occurred at the beginning of the second trimester with cystic hygroma in a case. In the first two males a miscarriage was observed also at the beginning of the second trimester after chorionic biopsy or amniocentesis. These two miscarriages would not be a complication of prenatal diagnosis but spontaneous abortion of an affected male. The date of the miscarriage of affected males (the beginning of the second trimester) and the role of a cystic hygroma for the diagnosis of incontinentia pigmenti in this mother of a fetus karyotyped 46,XY are discussed.
Subject(s)
Abortion, Spontaneous/etiology , Incontinentia Pigmenti/genetics , Abortion, Induced , Adult , Amniocentesis , Chorionic Villi Sampling , Female , Fetal Death/etiology , Fetal Diseases/diagnostic imaging , Fetal Diseases/genetics , Gestational Age , Humans , Incontinentia Pigmenti/diagnostic imaging , Karyotyping , Lymphangioma, Cystic/diagnostic imaging , Lymphangioma, Cystic/genetics , Male , Molecular Biology , Pregnancy , Pregnancy Trimester, Second , Sex Factors , Ultrasonography, PrenatalABSTRACT
BBB syndrome and G syndrome were originally reported as distinct X-linked disorders. Clinical studies indicated that BBB and G syndromes were likely to represent variant expression of the same disorder, now referred to as "Opitz" GBBB syndrome. Several occurrences of male-to-male transmission in both syndromes led to the hypothesis that GBBB syndrome was a single autosomal dominant, sex influenced disorder, now tentatively mapped to 5p12-13. We report on a large pedigree in which GBBB syndrome appears to cosegregate with a pericentric inversion of the X chromosome inv(X)(p22.3q26). It indicates the possible existence of a true X-linked form of GBBB syndrome, which does not appear phenotypically different from its autosomal counterpart. The gene could map in the vicinity of the breakpoints, in Xp or Xq. The existence of two genes affecting a common pathogenetic pathway could explain the gender-dependent expressivity of GBBB phenotype.
Subject(s)
Abnormalities, Multiple/genetics , X Chromosome , Chromosome Banding , Female , Genetic Linkage , Humans , Karyotyping , Male , Pedigree , SyndromeABSTRACT
In a 20-year-old primiparous patient, a routine ultrasound scan performed at 28 weeks revealed fetal ascites, bilateral talipes, and oligohydramnios. This woman, married to possibly her first cousin, was at risk for an autosomal recessive disease, a metabolic disorder. At 29 weeks, an amniotic fluid biochemical study revealed the presence of an abnormal band of free sialic acid, leading to a diagnosis of a congenital form of sialic acid storage disease. Termination of pregnancy was performed at 30 weeks. Measurement of free sialic acid in cultured fetal skin fibroblasts confirmed the diagnosis.
Subject(s)
Ascites/diagnosis , Fetal Diseases/diagnosis , Lysosomal Storage Diseases/diagnosis , Oligohydramnios/diagnosis , Sialic Acids/metabolism , Adult , Amniocentesis , Ascites/diagnostic imaging , Ascites/etiology , Cells, Cultured , Consanguinity , Facies , Female , Fetal Diseases/diagnostic imaging , Fibroblasts/metabolism , Humans , Liver/ultrastructure , Lysosomal Storage Diseases/diagnostic imaging , N-Acetylneuraminic Acid , Oligohydramnios/diagnostic imaging , Oligohydramnios/etiology , Pregnancy , Ultrasonography, PrenatalABSTRACT
Two groups of infertile men with obstructive azoospermia were screened for cystic fibrosis (CF) gene mutations (delta F508, exons 3, 4, 7, 10, 11, 14a, 17b, 19, 20, 21). The first group was composed of 26 patients with congenital agenesis of vas deferens (CAVD). The second group was composed of 12 patients with obstructive azoospermia associated with chronic suppurating respiratory disease (Young's syndrome). Of the group with CAVD, 77% of patients showed at least one mutation in the CF transmembrane conductance regulator (CFTR) gene. The delta F508 mutation occurred most frequently (54%), and the second most frequent mutation to occur was R117H (27%). Six patients were double heterozygotes. In Young's syndrome, no CF mutations were detected. CAVD can be considered as an incomplete clinical form of CF. However, the differences observed in CF mutations between CF and CAVD suggest that they are different disorders resulting from mutations in the same gene. Young's syndrome is a very different clinical entity.
Subject(s)
Bronchiectasis/complications , Membrane Proteins/genetics , Mutation , Oligospermia/complications , Oligospermia/genetics , Vas Deferens/abnormalities , Adult , Cystic Fibrosis/metabolism , Cystic Fibrosis Transmembrane Conductance Regulator , Humans , Male , SyndromeABSTRACT
BACKGROUND: The effects of volume expansion on the cardiac output (CO) of newborns have not been studied, so that the indications for colloid infusion are not well standardized. POPULATION AND METHODS: Twenty one newborns (14 preterm and seven term babies) were studied before the 7th day of life. Thirteen had patent ductus arteriosus (PDA) and six had ischemic cardiopathy. Hemodynamic data indicated that these babies should be given 20 ml/kg of a 10% albumin solution. Pulsed-wave Doppler echocardiography was performed before and after infusion. RESULTS: Only 11 newborns had initial low Co (less than 260 ml/kg/min in patients with PDA; less than 200 ml/kg/min in the others). The increases in CO (31 +/- 25% vs 7 +/- 11%, P < 0.01) and of mean aortic flow velocity (MAFV) (34.6 +/- 19.5% vs 7.2 +/- 6.1%, P < 0.01) were significantly greater in this group. The increases in mean arterial pressure (+4 +/- 5 mmHg) and CO (+20 +/- 18%) were significant (P < 0.01) for all patients, both premature and term (with or without PDA and ischemic cardiopathy). The increase in CO was correlated with the initial CO and the cutaneous refilling time but was not correlated with the increase in arterial pressure. The sizes of the ventricles and left atrium grew significantly but that of the right atrium did not. Analysis of the increase in stroke volume in terms of the end diastolic diameter of the left ventricle indicated that the cardiac reserves varied according to the Starling relation. CONCLUSION: Evaluation of MAFV and CO plus diagnosis of PDA are all needed in order to assess whether volume expansion is accurate or not, since, clinical data obtained during the neonatal period are insufficient to do this.
Subject(s)
Albumins/administration & dosage , Cardiac Output , Echocardiography, Doppler , Cardiac Volume , Ductus Arteriosus, Patent/diagnostic imaging , Ductus Arteriosus, Patent/physiopathology , Humans , Infant, Newborn , Myocardial Ischemia/diagnostic imaging , Myocardial Ischemia/physiopathologyABSTRACT
We report our experience of 15 cases of gastroschisis which occurred between 1981 and 1993. All but one were diagnosed antenatally by ultrasound between 16 and 32 weeks of pregnancy. We made a termination of the pregnancy in 3 cases, for multiple malformations in 2 cases and one case of very early premature rupture of the membranes (PROM). When checked (11 cases), the karyotype was normal. We made a cesarean section in 11 cases: the indication was a complication for 6 (fetal distress, PROM, polyhydramnios, large dilatation of the gut). We noted growth retardation in 7 newborns and prematurity in 5/12 (mean gestational age of 36.8 weeks). The preoperative study of the gut noted 5 cases with intestinal damage and one case of complete necrosis of the gut. The global prognosis is not as good as usual, with a perinatal mortality of 41.6% (5/12). We discuss this latter point and examine the literature.
Subject(s)
Abdominal Muscles/abnormalities , Fetal Diseases/diagnosis , Prenatal Diagnosis , Abdominal Muscles/surgery , Amniocentesis , Congenital Abnormalities/diagnosis , Congenital Abnormalities/genetics , Female , Fetal Diseases/diagnostic imaging , Fetal Diseases/genetics , Humans , Infant, Newborn , Karyotyping , Pregnancy , Pregnancy Outcome , Prognosis , Retrospective Studies , Ultrasonography, PrenatalABSTRACT
Linkage data for familial incontinentia pigmenti (IP2) and 17 X chromosomal markers are reported. The linkage previously found between IP2 and the F8C locus is confirmed (Z max = 11.85 at theta = 0.028). Linkage is established with distal markers DXS1108 (Z max = 10.06 at theta = 0.00) and DXYS154 (Z = 9.07 at theta = 0.019). Multipoint analysis supports the distal localization of the IP2 gene with respect to the F8C locus.
Subject(s)
Genes , Incontinentia Pigmenti/genetics , X Chromosome , Animals , Chromosome Mapping , Eye Abnormalities/genetics , Female , Genetic Markers , Humans , Lod Score , Male , Mice , Pedigree , Species SpecificityABSTRACT
Oculo-dento-digital syndrome (SODD) as defined by Meyer-Schwickerath in 1957 is a rare entity (84 cases) which belongs to ectodermal dysplasias. It consists of: the characteristic features (long face, pinched nose); syndactyly; ocular, dental and bone abnormalities. This entity is usually transmitted on the autosomal dominant mode. We report two cases (a mother and daughter) with polymalformations which we classed as SODD. Furthermore, agenesis of lacrimal duct and genitourinary abnormalities were noted. The mother had a very particular complex hair shaft dysplasia (incomplete pili torti, "tiger tail" aspect, fractures) with alopecia since she was fifteen years old. The daughter's hair was normal at birth. In SODD, fine and sparse hair is often observed (44 p. 100). Only one patient had hair shaft investigation under polarized light: pili annulati and monilethrix were described but not found in our cases. These two reports incite to the systematic hair shaft study in SODD as other ectodermal dysplasia syndromes.
Subject(s)
Abnormalities, Multiple , Eye Abnormalities , Hair Diseases/genetics , Hair/ultrastructure , Odontodysplasia/genetics , Syndactyly/genetics , Adult , Eye Abnormalities/complications , Female , Fingers/abnormalities , Hair/pathology , Hair Diseases/complications , Hair Diseases/pathology , Humans , Infant, Newborn , Odontodysplasia/complications , Syndactyly/complications , Syndrome , Toes/abnormalitiesABSTRACT
The authors report Larsen Syndrome in a male newborn with severe cervical spine malformations: segmentation abnormalities of the cervical spine and atlanto-axial dislocation. The severity of the cervical malformations occurring more often in the autosomal recessive form is emphasized.
Subject(s)
Abnormalities, Multiple/genetics , Cervical Vertebrae/abnormalities , Chromosome Aberrations/genetics , Facial Bones/abnormalities , Abnormalities, Multiple/diagnosis , Atlanto-Occipital Joint/abnormalities , Atlanto-Occipital Joint/pathology , Cervical Vertebrae/pathology , Chromosome Disorders , Facial Bones/pathology , Hip Dislocation, Congenital/diagnosis , Hip Dislocation, Congenital/genetics , Humans , Infant , Infant, Newborn , Joint Dislocations/genetics , Magnetic Resonance Imaging , Male , SyndromeABSTRACT
Previous linkage analysis of families with X-linked severe combined immunodeficiency (SCIDX1) mapped this locus to a large region encompassing about 10 to 20 cM at Xq12-21. We have analyzed in SCIDX1 families the segregation of 7 highly polymorphic microsatellites repeats localized to this region, including a new polymorphic microsatellite at the DXS135 locus described in this study, to refine the mapping of this disease locus. The observations of genetic recombinants within the previously defined SCIDX1-region allow us to establish new flanking markers at the DXS135 and DXS227 loci, which significantly reduce the region harboring the SCIDX1 locus to a distance estimated between 3 to 5 cM. The existence of multiple, highly polymorphic markers in the refined SCIDX1 region will greatly improve the accuracy of carrier detection and prenatal diagnosis for SCIDX1.
Subject(s)
Severe Combined Immunodeficiency/genetics , X Chromosome , Alleles , Base Sequence , Chromosome Mapping , Cosmids , DNA, Satellite/genetics , Female , Gene Library , Genetic Markers , Heterozygote , Humans , Male , Molecular Sequence Data , Pedigree , Polymorphism, Genetic , Recombination, Genetic , Repetitive Sequences, Nucleic AcidABSTRACT
The cystic fibrosis (CF) gene has been cloned and a major mutation identified (delta F508). This 3-bp deletion has been found in approximately 70% of CF chromosomes. We have used the strategy of denaturing gradient gel electrophoresis followed by direct sequencing of the polymerase chain reaction products, in order to detect other mutations in exons 10, 11 and 20 of the CF transmembrane conductance regulator gene. A new mutation, F1286-S, was found in exon 20. It involves a nucleotide change of T-->C at nucleotide 3989 and changes a phenylalanine into serine at position 1286 of the protein.