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Biomedical subjects

S Odent

Publications and source records attributed to S Odent.

At least 37 records · Page 2Linked to original sources
PubMed2000

Multi-minicore disease--searching for boundaries: phenotype analysis of 38 cases.

Multi-minicore disease (MmD) is a congenital myopathy morphologically defined by the presence of multiple small zones of sarcomeric disorganization and lack of oxidative activity ("minicores") in muscle fibers. The dinical expression of MmD is considered to be greatly variable, and the morphological lesions are nonspecific; therefore, its boundaries are poorly defined, and its molecular bases are not known. To better define the phenotypic characteristics of MmD, we analyzed a large series of 38 patients with multiple minicores in muscle fibers in the absence of any other potential cause. According to clinical features, 4 subgroups were identified. Most patients (30 cases) shared a common highly consistent phenotype marked by the axial predominance of muscle weakness and a high occurrence of severe respiratory insufficiency and scoliosis ("classical" form). Other forms were characterized by pharyngolaryngeal involvement and total lack of head control (2 cases), antenatal onset with arthrogryposis (3 cases), and slowly progressive weakness with marked hand amyotrophy (3 cases). Type 1 fiber predominance and hypotrophy as well as centrally located nuclei were found in every subgroup. MmD is thus phenotypically heterogeneous, but a typical recognizable phenotype does exist. This phenotype classification should be helpful when undertaking research into the molecular defects that cause MmD.

Biopsy↗
PubMed1999

Paracentric inversion of the X chromosome [inv(X)(q12q28)] in familial FG syndrome.

FG syndrome is an X-linked incomplete recessive condition comprising mental retardation, congenital hypotonia, macrocephaly, a distinctive facial appearance, and constipation or anal malformations. Here, we report on a chromosome X inversion [inv(X)(q12q28)] in a boy with FG syndrome and in his mentally retarded maternal uncle, and we discuss the possible involvement of this paracentric inversion in the FG syndrome.

Abnormalities, Multiple↗
PubMed1999

Heterotaxy-neural tube defect and holoprosencephaly occuring independently in two sib fetuses.

We report on two sib fetuses, products of a consanguineous union, who had multiple and apparently unrelated malformations. The first fetus, a female, had trilobed lungs, a single cardiac ventricle, asplenia, situs ambiguus of the liver, and a lumbosacral meningomyelocele. The brain of this fetus was normal. The second fetus, a male, had bilobed lungs, a single cardiac ventricle, situs solitus of the abdominal organs and spleen, and a semilobar holoprosencephaly. The occurrence of these malformations in sibs of different sexes and the parental consanguinity suggest a recessive mutation in a gene responsible for both heterotaxy and midline defects, including holoprosencephaly.

Female↗
PubMed1999

Mutations in the nebulin gene associated with autosomal recessive nemaline myopathy.

The congenital nemaline myopathies are rare hereditary muscle disorders characterized by the presence in the muscle fibers of nemaline bodies consisting of proteins derived from the Z disc and thin filament. In a single large Australian family with an autosomal dominant form of nemaline myopathy, the disease is caused by a mutation in the alpha-tropomyosin gene TPM3. The typical form of nemaline myopathy is inherited as an autosomal recessive trait, the locus of which we previously assigned to chromosome 2q21.2-q22. We show here that mutations in the nebulin gene located within this region are associated with the disease. The nebulin protein is a giant protein found in the thin filaments of striated muscle. A variety of nebulin isoforms are thought to contribute to the molecular diversity of Z discs. We have studied the 3' end of the 20. 8-kb cDNA encoding the Z disc part of the 800-kDa protein and describe six disease-associated mutations in patients from five families of different ethnic origins. In two families with consanguineous parents, the patients were homozygous for point mutations. In one family with nonconsanguineous parents, the affected siblings were compound heterozygotes for two different mutations, and in two further families with one detected mutation each, haplotypes are compatible with compound heterozygosity. Immunofluorescence studies with antibodies specific to the C-terminal region of nebulin indicate that the mutations may cause protein truncation possibly associated with loss of fiber-type diversity, which may be relevant to disease pathogenesis.

Australia↗
PubMed1999

Identification of a D579G homozygote cystic fibrosis patient with pancreatic sufficiency and minor lung involvement. Mutations in brief no. 221. Online.

Here we describe the identification of an italian patient homozygote for the D579G mutation affected by a mild form of Cystic Fibrosis with pancreatic sufficiency, minor lung involvement and marked viscosity of the cervical mucous. The D579G mutation causes an A1868G transition, a substitution of an aspartic acid to a glycine residue, generating an important amino acid change (charged to hydrophobic) in the nucleotide-binding domain (NBD). The mutation was first described by Brancolini et al. (1995) on two pancreatic sufficient CF patients, compound heterozygotes for delta508F. Patients were from Southern Italy (Puglia) as the D579G homozygote one, who is a 30 years old woman from Taranto (Puglia), daughter of second cousins born in Bari (Puglia). The identification of a homozygote D579G patient might confirm that this mutation does correlate with pancreatic sufficiency and a mild pulmonary phenotype.

Adult↗
PubMed1999

Expression of the Sonic hedgehog (SHH ) gene during early human development and phenotypic expression of new mutations causing holoprosencephaly.

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.

Brain↗
PubMed1999

Unusual fan shaped ossification in a female fetus with radiological features of boomerang dysplasia.

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.

Bone and Bones↗
PubMed1999

Gastric carcinoma in Sotos syndrome (cerebral gigantism).

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.

Adult↗
PubMed1998

Segregation analysis in nonsyndromic holoprosencephaly.

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.

Diseases in Twins↗
PubMed1998

Central nervous system malformations and early end-stage renal disease in oro-facio-digital syndrome type I: a review.

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.

Central Nervous System Diseases↗
PubMed1998

Identification of novel L1CAM mutations using fluorescence-assisted mismatch analysis.

The L1CAM gene, which is located in Xq28 and codes for a neuronal cell adhesion molecule, is involved in three distinct conditions: HSAS (hydrocephalus-stenosis of the aqueduct of Sylvius), MASA (mental retardation, aphasia, shuffling gait, adductus thumbs), and SPG1 (spastic paraplegia). Molecular analysis of the L1CAM gene is labor-intensive because of the size of the coding region, which is fragmented in numerous exons, and because of the great allelic heterogeneity and distribution of the mutations. The FAMA (fluorescent assisted mismatch analysis) method combines the excellent sensitivity of the chemical cleavage method for scanning PCR fragments larger than 1 kb and the power of automated DNA sequencers. In order to optimize this method for L1CAM, we divided the gene into nine genomic fragments, each including three to four exons. These fragments were PCR-amplified using nine sets of primers containing additional rare universal sequences. A second-stage PCR, per formed with the two dye-labeled universal primers, allowed us to generate 1-kb-labeled fragments, which were then submitted to the chemical cleavage analysis. Among 12 French families with HSAS and/or MASA, we identified nine distinct L1CAM mutations, seven of which were novel, and an intronic variation. This study demonstrates that FAMA allows rapid and reliable detection of mutations in the L1CAM gene and thus represents one of the most appropriate methods to provide diagnosis for accurate genetic counseling in families with HSAS, MASA, or SPG1.

Aphasia↗
PubMed1998

Mapping of a congenital microcoria locus to 13q31-q32.

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.

Chromosome Mapping↗
PubMed1997

Features of DiGeorge syndrome and CHARGE association in five patients.

We report on five patients presenting with features of two congenital disorders, DiGeorge syndrome (DGS) and CHARGE association. CHARGE association is usually sporadic and its origin is as yet unknown. Conversely, more than 90% of DGS patients are monosomic for the 22q11.2 chromosomal region. In each of the five patients, both cytogenetic and molecular analysis for the 22q11.2 region were normal. In view of the broad clinical spectrum and the likely genetic heterogeneity of both disorders, these cases are consistent with the extended phenotype of either DGS without 22q11.2 deletion or CHARGE association, especially as several features of CHARGE association have been reported in rare patients with 22q11.2 deletion association phenotypes. On the other hand, these could be novel cases of an independent association involving a complex defect of neural crest cells originating from the pharyngeal pouches.

Abnormalities, Multiple↗
PubMed1997

Prenatal detection of a congenital pancreatic cyst and Beckwith-Wiedemann syndrome.

We report a case of congenital pancreatic cyst detected prenatally by ultrasound in a fetus with evidence for a diagnosis of Beckwith-Wiedemann syndrome (BWS). Neonatal hypoglycaemia was prevented. The cyst was managed by internal drainage. This is the second reported case of BWS associated with pancreatic cystic dysplasia and the first time that this association has been detected prenatally. Differential diagnosis of cystic abdominal lesions occurring in utero should take pancreatic cysts into consideration. This case suggests that pancreatic cysts should be included in the BWS phenotype.

Adult↗
PubMed1997

[Spontaneous abortion of male fetuses with incontinentia pigmenti (apropos of a family)].

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.

Abortion, Induced↗
PubMed1996

Isolated X-linked thrombocytopenia in two unrelated families is associated with point mutations in the Wiskott-Aldrich syndrome protein gene.

The Wiskott-Aldrich syndrome (WAS) is characterized by defective platelet and lymphocyte function associated with eczema and increased susceptibility to malignancies. It is caused by mutations of the WAS protein-encoding gene (WASP). X-lined thrombocytopenia, defined by low platelet counts and volume, may be an allelic variant of WAS. In patients with XLT from two unrelated families, WASP gene defects were identified by single-strand conformational polymorphism and by sequencing. Point mutations in exon 2 of the WASP gene were found in the patients from both families in which XLT segregated. Several obligate heterozygote female members of these families display a random pattern of X inactivation in their peripheral blood leukocytes. This study shows that XLT may be caused by mutations of the WASP, thus representing an allelic variant of WAS.

Adult↗
PubMed1995

Opitz GBBB syndrome: chromosomal evidence of an X-linked form.

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.

Abnormalities, Multiple↗