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V Cormier-Daire

Publications and source records attributed to V Cormier-Daire.

At least 37 records · Page 2Linked to original sources
PubMed2003

Neurological presentation in pediatric patients with congenital disorders of glycosylation type Ia.

OBJECTIVE: Congenital disorders of glycosylation (CDG), formerly called carbohydrate-deficient glycoprotein syndromes, constitute a newly identified group of multisystem disorders characterized by defective glycosylation of N-glycosylated proteins. The objective of this work was to describe precisely neurological findings in patients with type Ia CDG (CDG-Ia) and to compare our results with the literature. STUDY DESIGN: We retrospectively reviewed neurological and neurodevelopmental, neuroimaging, and genetic features in ten patients with CDG-Ia who mainly presented with neurological abnormalities during childhood and therefore were referred to a neuropediatrician or a neurogeneticist. RESULTS: Neurological manifestations had a static clinical course, dominated by mental retardation and cerebellar dysfunction, and acute episodes: stroke-like episodes and seizures. However, microcephaly, retinopathy, and polyneuropathy were progressive. All patients had severe global neurodevelopmental delay: only one was able to walk alone at ten years of age and only one could read. Marked heterogeneity in manifestations and delay of diagnosis was noted across the patients. Cerebellar hypoplasia was found by magnetic resonance imaging in all ten patients and olivopontocerebellar hypoplasia in four patients. As in the literature, there was no clear phenotype-mutation correlation. CONCLUSION: Our findings confirm the importance of a precise and complete description of the neurological and neuroradiological phenotype delineating the phenotype of CDG-Ia to increase the likelihood of diagnosing the disease.

Adolescent↗
PubMed2003

In frame fibrillin-1 gene deletion in autosomal dominant Weill-Marchesani syndrome.

Weill-Marchesani syndrome (WMS) is a connective tissue disorder characterised by short stature, brachydactyly, joint stiffness, and characteristic eye anomalies including microspherophakia, ectopia of the lenses, severe myopia, and glaucoma. Both autosomal recessive (AR) and autosomal dominant (AD) modes of inheritance have been described and a gene for AR WMS has recently been mapped to chromosome 19p13.3-p13.2. Here, we report on the exclusion of chromosome 19p13.3-p13.2 in a large AD WMS family and show that, despite clinical homogeneity, AD and AR WMS are genetically heterogeneous entities. Because two AD WMS families were consistent with linkage to chromosome 15q21.1, the fibrillin-1 gene was sequenced and a 24 nt in frame deletion within a latent transforming growth factor-beta1 binding protein (LTBP) motif of the fibrillin-1 gene was found in a AD WMS family (exon 41, 5074_5097del). This in frame deletion cosegregated with the disease and was not found in 186 controls. This study strongly suggests that AD WMS and Marfan syndrome are allelic conditions at the fibrillin-1 locus and adds to the remarkable clinical heterogeneity of type I fibrillinopathies.

Abnormalities, Multiple↗
PubMed2003

The mitochondrial DNA G13513A MELAS mutation in the NADH dehydrogenase 5 gene is a frequent cause of Leigh-like syndrome with isolated complex I deficiency.

Leigh syndrome is a subacute necrotising encephalomyopathy frequently ascribed to mitochondrial respiratory chain deficiency. This condition is genetically heterogeneous, as mutations in both mitochondrial (mt) and nuclear genes have been reported. Here, we report the G13513A transition in the ND5 mtDNA gene in three unrelated children with complex I deficiency and a peculiar MRI aspect distinct from typical Leigh syndrome. Brain MRI consistently showed a specific involvement of the substantia nigra and medulla oblongata sparing the basal ganglia. Variable degrees of heteroplasmy were found in all tissues tested and a high percentage of mutant mtDNA was observed in muscle. The asymptomatic mothers presented low levels of mutant mtDNA in blood leucocytes. This mutation, which affects an evolutionary conserved amino acid (D393N), has been previously reported in adult patients with MELAS or LHON/MELAS syndromes, emphasising the clinical heterogeneity of mitochondrial DNA mutations. Since the G13513A mutation was found in 21% of our patients with Leigh syndrome and complex I deficiency (3/14), it appears that this mutation represents a frequent cause of Leigh-like syndrome, which should be systematically tested for molecular diagnosis in affected children and for genetic counselling in their maternal relatives.

Brain↗
PubMed2003

Homozygosity mapping of a Desbuquois dysplasia locus to chromosome 17q25.3.

Desbuquois dysplasia is a rare autosomal recessive chondrodysplasia characterised by short stature, joint laxity, facial dysmorphism, a "Swedish key" appearance of the proximal femur, advanced carpal and tarsal bone age, and hand anomalies consisting of phalangeal dislocations and an extra ossification centre distal to the second metacarpal. However, the latter changes are not consistently observed in all Desbuquois patients, defining two distinct groups, based on the presence or absence of hand anomalies. We have performed a genome wide search in four inbred Desbuquois families with typical hand anomalies originating from France, Sri-Lanka, the United Arab Emirates, and Morocco. Here, we report on the mapping of a disease gene to chromosome 17q25.3 (Zmax=4.61 at theta=0 at locus D17S1806) in the 9.5 cM interval defined by loci D17S802 and D17S1822. The present study supports the genetic homogeneity of the clinical subtype with hand anomalies and will hopefully help in identifying the Desbuquois dysplasia gene.

Chromosome Mapping↗
PubMed2003

Spectrum of NSD1 mutations in Sotos and Weaver syndromes.

Sotos syndrome is an overgrowth syndrome characterised by pre- and postnatal overgrowth, macrocephaly, advanced bone age, and typical facial features. Weaver syndrome is a closely related condition characterised by a distinctive craniofacial appearance, advanced carpal maturation, widened distal long bones, and camptodactyly. Haploinsufficiency of the NSD1 gene has recently been reported as the major cause of Sotos syndrome while point mutations accounted for a minority of cases. We looked for NSD1 deletions or mutations in 39 patients with childhood overgrowth. The series included typical Sotos patients (23/39), Sotos-like patients (lacking one major criteria, 10/39), and Weaver patients (6/39). We identified NSD1 deletions (6/33) and intragenic mutations (16/33) in Sotos syndrome patients. We also identified NSD1 intragenic mutations in 3/6 Weaver patients. We conclude therefore that NSD1 mutations account for most cases of Sotos syndrome and a significant number of Weaver syndrome cases in our series. Interestingly, mental retardation was consistently more severe in patients with NSD1 deletions. Macrocephaly and facial gestalt but not overgrowth and advanced bone age were consistently observed in Sotos syndrome patients. We suggest therefore considering macrocephaly and facial gestalt as mandatory criteria for the diagnosis of Sotos syndrome and overgrowth and advanced bone age as minor criteria.

Abnormalities, Multiple↗
PubMed2003

Adrenal insufficiency and abnormal genitalia in a 46XX female with Smith-Lemli-Opitz syndrome.

OBJECTIVE: To report the first case of a 46XX female infant with Smith-Lemli-Opitz syndrome (SLOS), adrenal insufficiency and abnormal genitalia. METHODS: The patient was assessed for hormonal status on day 4 and 6 months later and was followed-up from the study time (2.5 years of age). RESULTS: The patient had a persistent urogenital sinus, posterior labial fusion without clitoromegaly. She presented with a salt-wasting syndrome on day 4. Adrenal insufficiency was confirmed. Adrenal androgen levels, including 17-hydroxyprogesterone and 11-deoxycortisol were moderately elevated. CONCLUSION: Children with SLOS should be assessed for adrenal insufficiency. In female infants, abnormal external genitalia can be observed even if the precise mechanism behind these abnormalities is yet to be determined.

Abnormalities, Multiple↗
PubMed2002

Clinical and genetic heterogeneity of Seckel syndrome.

Seckel syndrome is a rare autosomal recessive condition belonging to the group of osteodysplastic primordial "dwarfism" and characterized by the association of 1) severe pre- and postnatal growth retardation, 2) microcephaly with mental retardation, and 3) specific dysmorphic features. Recently, two disease loci have been mapped to chromosomes 3q22.1-q24 and 18p11.31-q11.2, respectively, by homozygosity mapping in consanguineous families. Here, we report on the exclusion of these loci in five consanguineous and one multiplex nonconsanguineous Seckel syndrome families and in two consanguineous families presenting type II osteodysplastic primordial dwarfism. These results support the view that Seckel syndrome is a clinically and genetically heterogeneous condition.

Abnormalities, Multiple↗
PubMed2002

Homozygosity mapping of a Dyggve-Melchior-Clausen syndrome gene to chromosome 18q21.1.

Dyggve-Melchior-Clausen syndrome (DMC) is an autosomal recessive condition characterised by short trunk dwarfism, scoliosis, microcephaly, coarse facies, mental retardation, and characteristic radiological features. X rays show platyspondyly with double vertebral hump, epiphyseal dysplasia, irregular metaphyses, and a characteristic lacy appearance of the iliac crests. Electron microscopy of chondrocytes have shown widened cisternae of rough endoplasmic reticulum and biochemical analyses have shown accumulation of glucosaminoglycan in cartilage, but the pathogenesis of DMC remains unexplained. Here, we report on the homozygosity mapping of a DMC gene to chromosome 18q21.1 in seven inbred families (Zmax=9.65 at theta=0 at locus D18S1126) in the genetic interval (1.8 cM) defined by loci D18S455 and D18S363. Despite the various geographical origins of the families reported here (Morocco, Tunisia, Portugal, and Lebanon), this condition was genetically homogeneous in our series. Continuing studies will hopefully lead to the identification of the disease causing gene.

Abnormalities, Multiple↗
PubMed2002

Automated fluorescent genotyping detects 10% of cryptic subtelomeric rearrangements in idiopathic syndromic mental retardation.

Recent studies have shown that cryptic unbalanced subtelomeric rearrangements contribute to a significant proportion of idiopathic syndromic mental retardation cases. Using a fluorescent genotyping based strategy, we found a 10% rate of cryptic subtelomeric rearrangements in a large series of 150 probands with severe idiopathic syndromic mental retardation and normal RHG-GTG banded karyotype. Fourteen children were found to carry deletions or duplications of one or more chromosome telomeres and two children had uniparental disomy. This study clearly shows that fluorescent genotyping is a sensitive and cost effective method that not only detects cryptic subtelomeric rearrangements but also provides a unique opportunity to detect uniparental disomies. We suggest giving consideration to systematic examination of subtelomeric regions in the diagnostic work up of patients with unexplained syndromic mental retardation.

Child↗
PubMed2001

Phenotypic variability at the TGF-beta1 locus in Camurati-Engelmann disease.

Camurati-Engelmann disease (CED) [OMIM 131300] is an autosomal dominant sclerosing bone dysplasia recently ascribed to mutations of the transforming growth factor (TGF-beta1) gene on chromosome 19q13.1-q13.3. Five mutations consistently located in the TGF-beta1 propeptide have been hitherto identified in 21 families. Here, we report on TGF-beta1 mutations in one Australian and six European families. Three distinct mutations were identified among seven families: namely, R218H (family 1), R218C (families 2, 6, 7) and C225R (families 3, 4, 5). The three mutations identified in our pedigrees have been previously observed in families of Japanese and Israeli origin and the R218C appears to be the most prevalent mutation worldwide (17/28 reported families). No obvious correlation between the nature of the mutations and the severity of the clinical manifestations could be established, but a marked intrafamilial clinical variability was observed, supporting incomplete penetrance of CED. Interestingly, the polymorphisms in the TGF-beta1 gene showed no correlation with the severity of the disease. We conclude that CED is a clinically variable condition and that this clinical variability is not accounted for by polymorphisms at the TGF-beta1 locus.

Australia↗
PubMed2001

Severe mental retardation, short stature, facial anomalies, joint laxity, and dislocations in two sisters: previously undescribed MCA/MR syndrome.

We describe two sisters with short stature, obesity, "bulbous" nasal tip, microretrognathism, brachydactyly, joint hyperlaxity and dislocation, and mental retardation. Skeletal surveys disclosed widened mandibular angles, thin temporal processes, hypoplastic clavicles, short distal ends of ulnae, short fourth metacarpals, and dislocation of hips, elbows, and thumbs. The parents are first cousins. To the best of our knowledge, this combination of multiple congenital anomalies and mental retardation has not been reported before.

Abnormalities, Multiple↗