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C Goizet

Publications and source records attributed to C Goizet.

At least 19 recordsLinked to original sources
PubMed2006

SPG3A is the most frequent cause of hereditary spastic paraplegia with onset before age 10 years.

Seven families with six different SPG3A mutations were identified among 106 with autosomal dominant hereditary spastic paraplegia (HSP). Two mutations were novel (T162P, C375R). SPG3A was twice as frequent as SPG4 in patients with onset before age 10 years (31.8%). Later onset was not observed. The phenotype was pure HSP, but disease duration was longer than in non-SPG3A/SPG4 patients, leading ultimately to greater handicap.

Adolescent↗
PubMed2005

A second locus for Aicardi-Goutieres syndrome at chromosome 13q14-21.

BACKGROUND: Aicardi-Goutières syndrome (AGS) is an autosomal recessive, early onset encephalopathy characterised by calcification of the basal ganglia, chronic cerebrospinal fluid lymphocytosis, and negative serological investigations for common prenatal infections. AGS may result from a perturbation of interferon alpha metabolism. The disorder is genetically heterogeneous with approximately 50% of families mapping to the first known locus at 3p21 (AGS1). METHODS: A genome-wide scan was performed in 10 families with a clinical diagnosis of AGS in whom linkage to AGS1 had been excluded. Higher density genotyping in regions of interest was also undertaken using the 10 mapping pedigrees and seven additional AGS families. RESULTS: Our results demonstrate significant linkage to a second AGS locus (AGS2) at chromosome 13q14-21 with a maximum multipoint heterogeneity logarithm of the odds (LOD) score of 5.75 at D13S768. The AGS2 locus lies within a 4.7 cM region as defined by a 1 LOD-unit support interval. CONCLUSIONS: We have identified a second AGS disease locus and at least one further locus. As in a number of other conditions, genetic heterogeneity represents a significant obstacle to gene identification in AGS. The localisation of AGS2 represents an important step in this process.

Basal Ganglia Diseases↗
PubMed2005

Hereditary mucoepithelial dysplasia: clinical, ultrastructural and genetic study of eight patients and literature review.

BACKGROUND: Hereditary mucoepithelial dysplasia is a dominantly inherited disease, mainly characterized by chronic mucosal lesions associated with keratitis, non-scarring alopecia, keratosis pilaris and perineal intertrigo. Since the original report by Witkop, this condition has been considered to be a disorder of desmosome/gap junction formation, but there has been no ex vivo investigation of these components using genetic and immunolabelling techniques. OBJECTIVES: To perform light and immunoelectron microscopic studies, and partial genetic analysis on five patients in a family and three sporadic cases and to point out similarities of this rare disorder with chronic mucocutaneous candidiasis and other follicular keratosis syndromes, i.e. ichthyosis follicularis-alopecia-photophobia (IFAP), keratitis-ichthyosis-deafness (KID) and Siemens syndromes. METHODS: Biopsies from the involved oral mucosa and armpit skin of patient 1 were prepared for standard histopathology, electron microscopy and immunocytochemistry. Microsatellite genotyping was performed in three affected family members. Direct sequencing after polymerase chain reaction amplification of the entire coding region was performed. RESULTS: A 14-year-old male had recurrent keratitis, widespread keratosis pilaris, perineal intertrigo, hypotrichosis and oral mucosal involvement. A similar phenotype was noted in four members of his family and in three sporadic cases. Histological examination of oral mucosa and skin samples showed a psoriasiform pattern, dyskeratotic features and cytoplasmic vacuoles. Expression of connexins (Cx), desmosomal, adherens junction and cytoskeleton proteins (Cx 26, 32 and 43, desmogleins 1 and 2, plakoglobin, desmoplakins I-II, plakophilin 1, beta-catenin, E-cadherin, keratins, beta-tubulin, vimentin and actin) was normal. Ultrastructural studies showed a reduced number of desmosomes. Dyskeratotic cells exhibited internalized gap junctions, long filamentous inclusions reactive with antikeratin antibodies, and bundles of perinuclear fibres resembling clear tonofilaments. Genetic analysis in the studied family excluded the desmosomal cadherins in chromosome 18q12 as candidate genes. CONCLUSIONS: A diagnosis of hereditary mucoepithelial dysplasia should be strongly suggested by the triad of non-scarring alopecia, well-demarcated erythema of oral mucosa and psoriasiform perineal rash, after exclusion of the clinically related follicular keratosis syndromes. Defective expression of cytoskeleton elements and/or a modification of mechanisms regulating junction-cytoskeleton assembly may be primarily responsible for impaired epithelial cohesion.

Adolescent↗
PubMed2005

Mutations in PHF8 are associated with X linked mental retardation and cleft lip/cleft palate.

Truncating mutations were found in the PHF8 gene (encoding the PHD finger protein 8) in two unrelated families with X linked mental retardation (XLMR) associated with cleft lip/palate (MIM 300263). Expression studies showed that this gene is ubiquitously transcribed, with strong expression of the mouse orthologue Phf8 in embryonic and adult brain structures. The coded PHF8 protein harbours two functional domains, a PHD finger and a JmjC (Jumonji-like C terminus) domain, implicating it in transcriptional regulation and chromatin remodelling. The association of XLMR and cleft lip/palate in these patients with mutations in PHF8 suggests an important function of PHF8 in midline formation and in the development of cognitive abilities, and links this gene to XLMR associated with cleft lip/palate. Further studies will explore the specific mechanisms whereby PHF8 alterations lead to mental retardation and midline defects.

Animals↗
PubMed2004

[Hereditary neuralgic amyotrophy: a paediatric and familial presentation of Parsonage-Turner syndrome].

Hereditary neuralgic amyotrophy is a rare disorder, characterized by recurrent attacks of pain in a brachial plexus distribution. We report the case of a 12-year-old boy with several attacks of pain and atrophy of the muscles of the shoulders. The age of onset of this disease is variable, most frequently in the second or third decade. Pediatric onsets, during the first decade are rare. The differences between the hereditary neuralgic amyotrophy and the sporadic Parsonage-Turner syndrome are painful recurrent episodes of weakness and similar familial cases. The analysis of several families has shown that hereditary neuralgic amyotrophy phenotype is heterogeneous and two different clinical courses can be discerned. Recent evidence indicates that HNA is genetically heterogeneous. Pathophysiology of the disease remains unclear, so the treatment is not clearly established.

Age of Onset↗
PubMed2004

Phenotypic heterogeneity in AAAS gene mutation.

UNLABELLED: We report the cases of two sibs of North African origin with AAAS gene mutation characterized by the heterogeneity of their phenotype. While an 8-y-old boy presented with acute adrenal insufficiency and mental retardation, the diagnosis was suggested by the clinical history of his 6-y-old sister who had symptomatic achalasia and chronic adrenal failure. CONCLUSION: Our observations corroborate the phenotypic heterogeneity reported in triple A syndrome, and underline the possibility of a variable intra-familial expression.

Adrenal Insufficiency↗
PubMed2002

Presymptomatic testing in Huntington's disease and autosomal dominant cerebellar ataxias.

OBJECTIVE: To report a 7-year experience of presymptomatic testing in persons at risk for Huntington disease (HD) and to compare their characteristics and outcomes with those of persons at risk for a less disabling condition, autosomal dominant cerebellar ataxias (ADCA). METHODS: The authors collected data on presymptomatic testing for HD (n = 712) and ADCA (n = 46) in 10 French centers. RESULTS: The characteristics of applicants were similar in HD and ADCA, revealing a predominance of women, a low rate of completing the presymptomatic testing program, and a high rate of follow-up. The frequency of serious events was low (2% for HD, 5% for ADCA), but such events were also found after favorable results. Family planning was a more frequent reason for seeking presymptomatic testing in ADCA than in HD. Prenatal diagnosis was performed in only half of the pregnancies in HD carriers (n = 35) but in all of those in ADCA carriers (n = 4). CONCLUSION: Counseling in multistep and multidisciplinary teams is important not only for presymptomatic testing in HD but also for less disabling diseases.

Adolescent↗
PubMed2002

Progressive bulbospinal amyotrophy in triple A syndrome with AAAS gene mutation.

Triple A (3A) syndrome, a rare autosomal recessive disorder, is characterized by adrenocorticotropic hormone-resistant adrenal insufficiency, achalasia of the cardia, alacrima, and variable autonomic and neurologic dysfunction. The gene responsible, AAAS, recently has been identified. We describe the neurologic phenotype of the first adult case of 3A syndrome presenting bulbospinal amyotrophy as the prominent sign in association with a homozygous nonsense mutation identified in the AAAS gene.

Adrenal Gland Diseases↗
PubMed2001

Infantile Alexander disease: spectrum of GFAP mutations and genotype-phenotype correlation.

Heterozygous, de novo mutations in the glial fibrillary acidic protein (GFAP) gene have recently been reported in 12 patients affected by neuropathologically proved Alexander disease. We searched for GFAP mutations in a series of patients who had heterogeneous clinical symptoms but were candidates for Alexander disease on the basis of suggestive neuroimaging abnormalities. Missense, heterozygous, de novo GFAP mutations were found in exons 1 or 4 for 14 of the 15 patients analyzed, including patients without macrocephaly. Nine patients carried arginine mutations (four had R79H; four had R239C; and one had R239H) that have been described elsewhere, whereas the other five had one of four novel mutations, of which two affect arginine (2R88C and 1R88S) and two affect nonarginine residues (1L76F and 1N77Y). All mutations were located in the rod domain of GFAP, and there is a correlation between clinical severity and the affected amino acid. These results confirm that GFAP mutations are a reliable molecular marker for the diagnosis of infantile Alexander disease, and they also form a basis for the recommendation of GFAP analysis for prenatal diagnosis to detect potential cases of germinal mosaicism.

Adolescent↗
PubMed2001

Histopathological features of X-linked Charcot-Marie-Tooth disease in 8 patients from 6 families with different connexin32 mutations.

There is still confusion as to whether X-linked Charcot-Marie-Tooth disease (CMTX) is primarily an axonal disorder or is primarily demyelinating. Eight symptomatic patients, 7 males and 1 female, from 6 families with identified connexin32 mutations underwent a superficial peroneal nerve biopsy. Quantitative and ultrastructural studies were performed, and histopathological lesions in these 8 patients proved to be quite homogeneous. The myelinated fiber count was within normal values or only moderately decreased. In 7 cases, the distribution of myelinated fibers was unimodal due to a loss of large fibers, coexisting with numerous clusters of small regenerating fibers. At ultrastructural level, these clusters were often surrounded by flattened Schwann cell processes giving an aspect of "pseudo-onion bulb" formation. There was no "naked axon" (ie, demyelinated axon), and real "onion bulb" formations composed of flattened Schwann cell processes surrounding an isolated myelinated fiber were discrete and not numerous. Macrophages laden with myelin debris were scarce or absent in the endoneurium. Several fibers appeared discretely hypomyelinated and the calculated g-ratio was scarcely higher than the mean control value. Lesions of unmyelinated fibers were absent in 7 cases and mild in one. Given that the primary defect concerns connexin32, we think that the histopathological features observed in our patients correspond to primary hypomyelination rather than to ongoing demyelination. The associated axonal degeneration might be secondary to defective axon-Schwann cell interactions.

Adolescent↗
PubMed2001

Leucodystrophy and oculocutaneous albinism in a child with an 11q14 deletion.

We report a patient with an undetermined leucodystrophy associated with type 1A oculocutaneous albinism (OCA). Type 1 OCA results from recessive mutations in the tyrosinase gene (TYR) located in 11q14.3. The patient was found by FISH to carry a deletion of at least the first exon of the TYR gene on one chromosome and a (TG) deletion at codon 244/245 on the second chromosome. The existence of the microdeletion suggested that a gene responsible for leucodystrophy was located in the vicinity of the TYR gene. A combination of a test of hemizygosity and contig mapping studies allowed us to map the gene within a 0.6 cM region flanked by microsatellite markers D11S1780 and D11S931.

Adolescent↗
PubMed2000

Case with autistic syndrome and chromosome 22q13.3 deletion detected by FISH.

Autism is a rare neurodevelopmental disorder with a strong genetic component. Co-occurrence of autism and chromosomal abnormalities is useful to localize candidate regions that may include gene(s) implicated in autism determinism. Several candidate chromosomal regions are known, but association of chromosome 22 abnormalities with autism is unusual. We report a child with autistic syndrome and a de novo 22q13.3 cryptic deletion detected by FISH. Previously described cases with 22q13.3 deletions shared characteristic developmental and speech delay, but autism was not specifically reported. This case emphasizes a new candidate region that may bear a gene involved in autism etiopathogenesis. Am. J. Med. Genet. (Neuropsychiatr. Genet.) 96:839-844, 2000.

Adolescent↗
PubMed2000

[Williams syndrome (microdeletion 7q11.23), model of behavioral phenotype].

A specific behavioral phenotype is recognized in some genetic entities, particularly in microdeletion syndromes secondary to cytogenetically undetectable chromosomal deletions. Williams syndrome (WS) is a developmental disorder displaying dysmorphic signs, heart malformations and behavioral phenotype associated, in most cases, with a deletion of chromosome 7q11.23. We described physical and neuro-psychological assessment of nine cases of SW. Molecular studies were performed using Southern blot analyses or FISH, and identified a 7q11.23 deletion in all cases. Behavioral phenotype of WS is characterized by hyperactivity, engaging and jovial personality, hypersensitivity in hearing, and some elements of speech may be enhanced. Moderate mental retardation is frequently present. Previously reported studies have revealed specific cognitive deficits including deficits in language development and in long term memory, and poor visual-motor integration. Two genes, LIMK1 and STX1A, have been supposed to be implicated in determinism of WS behavioral phenotype. A specific behavioral phenotype is also demonstrated in others microdeletion syndromes, focusing attention on some chromosomal regions supposed to contain candidate genes involved in cognitive and behavioral traits.

Adult↗
PubMed1999

W syndrome: report of three cases and review.

Only three cases of W syndrome have been reported. These patients have a typical "pugilistic" face, incomplete oral cleft, absent upper incisors, mental retardation, spasticity, seizures, and acne scars. Two of them had additional skeletal anomalies. Here we report on three male patients with findings compatible with the W syndrome. We emphasize the importance of some constant findings and describe additional signs. Familial history supports X-linked dominant heredity, as postulated previously.

Abnormalities, Multiple↗