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Biomedical subjects

G Ponsot

Publications and source records attributed to G Ponsot.

At least 55 records · Page 3Linked to original sources
PubMed1998

Congenital insensitivity to pain with anhydrosis. Report of two unrelated cases.

Two unrelated female cases of congenital insensitivity to pain with anhydrosis are presented. The first case was born from consanguineous parents. In both cases, onset of manifestation was observed in infancy with automutilation and recurrent fever. Both were mentally retarded. They underwent a peripheral nerve biopsy respectively at 3 and 33 years. A dramatic loss of unmyelinated fibers was observed in both cases. Myelinated fibers were also moderately reduced in number, especially those of smallest diameter; this loss was more marked in the second patient who was adult when the peripheral nerve was studied. Clusters of regenerating myelinated fibers were seen in both cases. Such histological observations might suggest a slowly progressive disorder. The cases are discussed together with previous reports dealing with congenital insensitivity to pain.

Adult↗
PubMed1997

Gene for nonspecific X-linked mental retardation (MRX 47) is located in Xq22.3-q24.

We describe a large family with nonspecific X-linked mental retardation (MRX 47). An X-linked recessive transmission is suggested by the inheritance from the mothers in two generations of a moderate to severe form of mental retardation in six males, without any specific clinical findings. Two point linkage analysis demonstrated significant linkage between the disorder and two markers in Xq23 (Zmax = 3.75, theta = 0). Multipoint linkage analyses confirmed the significant linkage with a maximum lod score (Z = 3.96, theta = 0) at DXS1059. Recombination events observed with the flanking markers DXS1105 and DXS8067 delineate a 17 cM interval. This interval overlaps with several loci of XLMR disorders previously localized in Xq23-q24, which are reviewed herein.

Chromosome Mapping↗
PubMed1997

Biochemical and genetic studies of four patients with pyruvate dehydrogenase E1 alpha deficiency.

We report studies of four patients with pyruvate dehydrogenase complex (PDH) deficiency caused by mutations in the E1 alpha subunit. Two unrelated male patients presented with Leigh syndrome and a R263G missense mutation in exon 8. This mutation has previously been described in males with the same phenotype. The two other patients had different novel mutations: (1) an 8-bp deletion at the C-terminus (exon 11) was found in one allele of a young girl suffering from microcephaly and (2) a C88S missense mutation (exon 3) in a boy who only presented with motor neuropathy. These mutations were not found in the mothers of any of the four cases. Immunoblot analysis revealed decreased immunoreactivity for the E1 alpha and E1 beta subunits in three out of the four patients. These findings confirm that: (1) PDH deficiencies are genetically heterogeneous, (2) the R263G mutation is more frequent in male cases than are other mutations and this amino acid is a hot spot for gene mutations, (3) the last eight amino acids may be important for the conformation of the tetrameric E1-PDH enzyme, and (4) the amino acids at positions 88, 263 and 382-387 are essential for the linking of the alpha subunit with the beta subunit and for the activity of the holoenzyme.

Adolescent↗
PubMed1997

A near homoplasmic T8993G mtDNA mutation in a patient with atypic Leigh syndrome not present in the mother's tissues.

We report an interesting case of a T8993G mutation in the muscle mtDNA of a 2-year-old girl who presented with myoclonia, developmental delay, increased lactate concentration in CSF and cerebral MRI abnormalities without retinopathy, suggesting an atypical form of Leigh syndrome. Search for mutant molecules in the blood and skin fibroblasts of the patient's healthy mother as well as in the blood of the also unaffected patient's sister was unsuccessful. This "sporadic' case of 8993 mtDNA mutation may be due either to a de novo mutation arising during oogenesis (or early embryogenesis) or to a mutation pre-existing in oocytes in a few mtDNA molecules and selected through a narrow bottleneck mechanism. Whatever the mechanism involved, this observation illustrates a complete shift of the mtDNA type in only one generation: from 0 to nearly 100% of mtDNA molecules with the T8993G mutation.

Child, Preschool↗
PubMed1997

Dominant X linked subcortical laminar heterotopia and lissencephaly syndrome (XSCLH/LIS): evidence for the occurrence of mutation in males and mapping of a potential locus in Xq22.

X linked subcortical laminar heterotopia and lissencephaly syndrome (XSCLH/ LIS) is an intriguing disorder of cortical development, which causes classical lissencephaly with severe mental retardation and epilepsy in hemizygous males, and subcortical laminar heterotopia (SCLH) associated with milder mental retardation and epilepsy in heterozygous females. Here we report an exclusion mapping study carried out in three unrelated previously described families in which males are affected with lissencephaly and females with SCLH, using 38 microsatellite markers evenly distributed on the X chromosome. Most of the X chromosome was excluded and potential intervals of assignment in Xq22.3-q23 or in Xq27 are reported. Although the number of informative meioses did not allow a decision between these two loci, it is worth noting that the former interval is compatible with the mapping of a breakpoint involved in a de novo X;autosomal balanced translocation 46,XX,t(X;2)(q22;p25) previously described in a female with classical lissencephaly. In addition, haplotype inheritance in two families showed a grandpaternal origin of the mutation and suggested in one family the presence of mosaicism in germline cells of normal transmitting males.

Adult↗
PubMed1997

A gene for dominant nonspecific X-linked mental retardation is located in Xq28.

A large family (MRX48) with a nonspecific X-linked mental retardation condition is described. An X-linked semidominant inheritance is suggested by the segregation in three generations of a moderate to severe mental retardation in seven males and by a milder intellectual impairment in two females, without any specific clinical, radiological, or biological feature. Two-point linkage analysis demonstrated significant linkage between the disorder and several markers in Xq28 (maximum LOD score [Zmax] = 2.71 at recombination fraction [theta] = 0); multipoint linkage analyses confirmed the significant linkage with a Zmax of 3.3 at theta = 0, at DXS1684. A recombination event observed with the flanking marker DXS8011 delineates a locus between this marker and the telomere. The approximate length of this locus is 8-9 cM, corresponding to 5.5-6 Mb. In an attempt to explain the variable intellectual impairment in females, we examined X-chromosome inactivation in all females of the family. Inactivation patterns in lymphocytes were random or moderately skewed, and no correlation between the phenotypic status and a specific inactivation pattern was observed. The interval of assignment noted in this family overlaps with five MRX loci previously reported in Xq28.

Adult↗
PubMed1996

Biochemical investigations and immunoblot analyses of two unrelated patients with an isolated deficiency in complex II of the mitochondrial respiratory chain.

Mitochondrial respiratory chain defects involving complex II are comparatively rare. We report the biochemical findings in two unrelated patients who both have an isolated complex II deficiency (40-50% of control values). Western blot analysis of mitochondrial fractions showed different findings between the two patients. In one patient there was a decrease in the levels of both the Fp and Ip subunits whereas in the other patient the levels of all immunoreactive complex II subunits were normal. This is the first time that an isolated deficiency of complex II activity associated with normal levels of protein subunits, using subunit specific antisera, has been described.

Blotting, Western↗
PubMed1996

Hypomelanosis of Ito and brain abnormalities: MRI findings and literature review.

We report the results of a 14-year retrospective study of brain MRI abnormalities in 12 pediatric patients presenting with hypomelanosis of Ito (HI). Miscellaneous brain abnormalities were found: one patient had a medulloblastoma, three had cortical malformations, and five demonstrated "minor" abnormalities such as dilated Virchow-Robin spaces or brain atrophy. We emphasize the polymorphism of brain abnormalities associated with HI.

Adolescent↗
PubMed1996

Recessive Schwartz-Jampel syndrome (SJS): confirmation of linkage to chromosome 1p, evidence of genetic homogeneity and reduction of the SJS locus to a 3-cM interval.

Schwartz-Jampel syndrome (SJS), or chondrodystrophic myotonia, is a rare autosomal recessive disorder characterized by generalized myotonia resulting in a particular, recognizable facies and osteoarticular abnormalities. Some of us have recently shown genetic linkage of SJS to a locus on 1p34-p36.1 in five families. Here, we show by homozygosity mapping and segregation analysis that eight new families are most likely linked to the SJS locus on chromosome 1, confirming the localization of SJS to chromosome 1p and suggesting genetic homogeneity. Recombination events reduced the SJS locus from a genetic interval of 8 to 3 cM, which should facilitate the identification of the SJS gene. Low clinical variability was observed between the studied families, except for osteoarticular abnormalities. Since the severity and the location of osteoarticular abnormalities varied from one individual to another, even in the same families, other factors than the SJS gene itself, genetic or epigenetic, might contribute to the phenotype.

Alleles↗
PubMed1996

A duplication of distal Xp associated with hypogonadotrophic hypogonadism, hypoplastic external genitalia, mental retardation, and multiple congenital abnormalities.

An unusual familial case of three sibs with a partial duplication of distal Xp sequences is described. The proband, an 18 year old boy, showed mental retardation, severe dysmorphic features, hypogonadotrophic hypogonadism (HHG), and hypoplastic external genitalia. His karyotype was 46,Y,inv dup(X) (p22.11-->p 22.32). The proband has two sisters each with the same inv dup(Xp) chromosome. Both sisters presented with short stature but were otherwise phenotypically normal. The abnormal X chromosome was inactive in the majority of cells examined. Southern blot dosage analysis indicated a duplication of distal Xp sequences. The proximal breakpoint is located between DXS28 and DXS41, and is therefore at least 2 Mb distal to the DSS locus. The relationship between the phenotype and the Xp duplication is discussed.

Abnormalities, Multiple↗
PubMed1996

[Corpus callosum agenesis and parasagittal interhemispheric cyst].

We report the association of a corpus callosum agenesis with a parasagittal interhemispheric cyst, without cortical malformation. This rare malformation is related to an early disorder in embryogenesis. The importance of the anatomic abnormalities compared with the good clinical status is remarkable. MR findings avoid misdiagnosis with a medial interhemispheric cyst associated to corpus callosum agenesis in which the prognosis is unpredictable.

Agenesis of Corpus Callosum↗
PubMed1995

Developmental aspects of type II lissencephaly. Comparative study of dysplastic lesions in fetal and post-natal brains.

We report neuropathological studies of five cases of type II lissencephaly from three fetuses and two infants. This comparative study allowed us to determine the developmental course of the cerebral lesions. Two distinct developmental events seem to generate this type of brain malformation: firstly, an early disturbance in cortex formation, which results both from a disorder of radial migration and a pial barrier disruption; secondly, a late perturbation of cerebral surface organization, resulting in fusion of the cerebral surface. All these features can be related to a primitive meningeal pathology, and more generally, to a neurocristopathy. Accordingly to our observations, this brain malformation appears during both migrational and post-migrational stages and may be considered more like a polymicrogyria than a lissencephaly.

Abnormalities, Multiple↗
PubMed1995

Clinical, biochemical, and molecular analysis of a maternally inherited case of Leigh syndrome (MILS) associated with the mtDNA T8993G point mutation.

We report a new case of Leigh disease (subacute necrotizing encephalomyelopathy) in a girl with mitochondrial DNA (mtDNA) mutation in the ATPase6 gene at nucleotide position 8993. Sequence analysis of mtDNA revealed a T-to-G transversion at nucleotide position 8993 in the ATPase6 gene. Southern blot restriction analysis of patient muscle mtDNA showed only a mutant pattern for the mutation 8993. Molecular analysis of seven subjects from the family showed that except for the father they all carried the 8993 mtDNA mutation in all studied tissues, with high percentages in the two symptomatic children and even in one asymptomatic boy.

Brain↗
PubMed1995

Localization of the Schwartz-Jampel syndrome (SJS) locus to chromosome 1p34-p36.1 by homozygosity mapping.

Schwartz-Jampel syndrome (SJS, MIM 255800), also known as chondrodystrophic myotonia, is a rare autosomal recessive disorder characterized by generalized myotonia, skeletal abnormalities and facial dysmorphism. Using homozygosity mapping, we localized the SJS locus to chromosome 1p34-p36.1 in a 8 cM interval flanked by markers D1S199 and D1S234. Families of different ethnic backgrounds (Tunisia and South Africa) showed genetic linkage to the same locus. Moreover, one Algerian family also demonstrated evidence of genetic linkage to 1p34-p36.1. Taken altogether, our results suggest genetic homogeneity, at least in the group of families analyzed.

Chromosome Mapping↗