Rare metabolic disease mimicking COL4A1/COL4A2 fetal brain phenotype.

Pathogenic variants of collagen type IV alpha 1 and 2 (COL4A1/COL4A2) genes cause various phenotypic anomalies, including intracerebral hemorrhage and a wide spectrum of developmental anomalies. Only 20% of fetuses referred for COL4A1/COL4A2 molecular screening (fetuses with a suspected intracerebral hemorrhage) carry a pathogenic variant in these genes, raising questions regarding the causative anomaly in the remaining 80% of these fetuses. We examined, following termination of pregnancy or in-utero fetal death, a series of 113 unrelated fetuses referred for COL4A1/COL4A2 molecular screening, in which targeted sequencing was negative. Using exome sequencing data and a gene-based collapsing test, we searched for enrichment of rare qualifying variants in our fetal cohort in comparison to the Genome Aggregation Database (gnomAD) control cohort (n = 71 702). Qualifying variants in pyruvate dehydrogenase E1 subunit alpha 1 (PDHA1) were overrepresented in our cohort, reaching genome-wide significance (P = 2.11 × 10-7 ). Heterozygous PDHA1 loss-of-function variants were identified in three female fetuses. Among these three cases, we observed microcephaly, ventriculomegaly, germinolytic pseudocysts, agenesis/dysgenesis of the corpus callosum and white-matter anomalies that initially suggested cerebral hypoxic-ischemic and hemorrhagic lesions. However, a careful a-posteriori reanalysis of imaging and postmortem data showed that the observed lesions were also consistent with those observed in fetuses carrying PDHA1 pathogenic variants, strongly suggesting that these two phenotypes may overlap. Exome sequencing should therefore be performed in fetuses referred for COL4A1/COL4A2 molecular screening which are screen-negative, with particular attention paid to the PDHA1 gene. © 2022 International Society of Ultrasound in Obstetrics and Gynecology.

Clinical Phenotype in an Early-Onset French Pediatric Population: Charcot-Marie-Tooth's Disease Type 2A.

Charcot-Marie-Tooth's disease type 2A (MCT2A), induced by mutation of the mitofusin 2 (MFN2) gene represents the main cause of MCT2. The aim of this study is to provide details of the clinical and electromyographic phenotype of MCT2A in a pediatric population. We conducted a French multicenter retrospective study, including all children with a genetic diagnosis of MCT2A. Thirteen MCT2A children were included with a beginning of symptoms before the age of 10 years ("early-onset group"). We report two new mutations: c.1070 A → T (p.Lys357.Met) and c.280 C → G (p.Arg94Gly). The evolution of the disease is marked by a fast worsening for three patients with loss of motor autonomy, while the evolution is relatively stable for eight patients. The group of early-onset MCT2A seems more heterogeneous than previously described, with a nonconstant severe phenotype.

Bilateral idiopathic calf muscle hypertrophy: an exceptional cause of unsightly leg curvature.

The authors present the management of a young female patient who presented with longstanding bilateral calf muscle hypertrophy, with no known cause. Taking into account the patient's wishes and the fact that the hypertrophy was mainly located in the posteromedial compartment, we chose to carry out a subtotal bilateral resection of medial gastrocnemius muscles. This procedure was performed with an harmonic scalpel, permitting a excellent cosmetic result while avoiding complications or functional impairment. After a reviewing of the commonly used techniques, the authors discuss the chosen surgical approach taking into account its clinical particularity.

Partial acute transverse myelitis is a predictor of multiple sclerosis in children.

BACKGROUND: Acute transverse myelitis (ATM) in children is a rare and often severe disease for which there are few known prognostic factors, particularly the subsequent risk of multiple sclerosis (MS) diagnosis. OBJECTIVES: To determine the clinical course and prognostic factors after a first episode of ATM in children. METHODS: Thirty children below 16 years of age diagnosed with a first neurological episode of ATM were included retrospectively. Clinical evaluation, treatment, laboratory, and MRI data were collected. RESULTS: Median age at onset was 11 years (range 3-15 years). Follow-up data were available for a median of 4 years (range 0.5-16.7 years). Five patients subsequently had a diagnosis of MS (17%), which was associated with acute partial transverse myelitis (odds ratio 5; 95% confidence interval 2.3-11), with a 60% probability of having a relapse at five years (p < 0.01). The 2011 Verhey criteria correctly identified MS in children with the highest specificity (96%) and sensitivity (80%). CONCLUSION: Acute partial transverse myelitis and brain MRI abnormalities at initial presentation are significantly predictive of a subsequent diagnosis of MS in children with ATM. These findings suggest that closer brain MRI monitoring after acute partial transverse myelitis might make the earlier introduction of disease-modifying therapies possible.

[Phenotypic heterogeneity and phenotype-genotype correlations in dystrophinopathies: Contribution of genetic and clinical databases]. / Variabilité phénotypique et corrélations génotype-phénotype des dystrophinopathies : contribution des banques de données.

The objective of this work was to study the natural history of dystrophinopathies and the genotype-phenotype correlations made possible by the development of the clinical part of the French DMD database. The collection of 70,000 clinical data for 600 patients with an average longitudinal follow-up of 12years enabled clarification of the natural history of Duchenne and Becker muscular dystrophies and clinical presentations in symptomatic females. We were able to specify the phenotypic heterogeneity of motor, orthopedic and respiratory involvements (severe, standard and intermediary form), of the cardiac disorder (severe, standard or absent cardiomyopathy, absence of correlation between motor and cardiac involvements), and of brain function (mental deficiency in the patients with Becker muscular dystrophy, psychopathological disorders in dystrophinopathies). Phenotypic variability did not correlate with a specific mutational spectrum. We propose a model of phenotypic analysis based on the presence or not of muscular and cardiac involvements (described by age at onset and rate of progression) and brain involvement (described by the type and the severity of the cognitive impairment and of the psychological disorders). The methodology developed for the DMD gene can be generalized and used for other databases dedicated to genetic diseases. Application of this model of phenotypic analysis for each patient and further development of the database should contribute substantially to clinical research providing useful tools for future clinical trials.

Prognostic value of contrast-enhanced MRI in Guillain-Barré syndrome in children.

BACKGROUND: The aim of this retrospective study is to explore the prognostic value of different contrast enhancement imaging patterns in childhood Guillain-Barré syndrome by comparing the clinical, laboratory, and therapeutic outcomes. METHODS: We included a total of 37 patients who were diagnosed and followed up by a pediatric neurology team at Montpellier University Hospital between 2000 and 2016. All images were reinterpreted by the first author and a senior pediatric neuroradiology staff member in two different sessions; in the case of disagreement, the expert's reading was considered. RESULTS: The study group comprised 22 (59.5%) boys and 15 (40.5%) girls. The age ranged from 1.5 year to 14.8 years. Muscle weakness was present in 33 (89.2%) patients. Cranial nerves involvement was observed in 22 (59.5%) patients, while 29 (78.4%) patients had albuminocytological dissociation. In 27 (73%) patients, contrast enhancement or thickening of the lumbosacral nerve roots was found. Simultaneous spinal nerve root and cranial nerve enhancement was noted in five (17.2%) patients, while isolated cranial nerve enhancement was identified in three (10.3%) patients. Clinical and radiological cranial nerve involvement was found in seven (18.9%) patients, while isolated clinical cranial nerves involvement occurred in 13 (35.1%) patients. No significant correlation between different magnetic resonance imaging (MRI) enhancement patterns and short-term or long-term outcomes was found in our cohort. CONCLUSION: Contrast-enhanced brain and spinal MRI is a sensitive and recommended supportive test for diagnosing acute inflammatory polyradiculopathy in children. Its predictive value for clinical, and therapeutic outcomes in the short or long term has not yet been proved.

Refinement of cortical dysgeneses spectrum associated with TUBA1A mutations.

OBJECTIVE: We have recently shown that de novo mutations in the TUBA1A gene are responsible for a wide spectrum of neuronal migration disorders. To better define the range of these abnormalities, we searched for additional mutations in a cohort of 100 patients with lissencephaly spectrum for whom no mutation was identified in DCX, LIS1 and ARX genes and compared these data to five previously described patients with TUBA1A mutations. RESULTS: We detected de novo TUBA1A mutations in six patients and highlight the existence of a prominent form of TUBA1A related lissencephaly. In four patients, the mutations identified, c.1190T>C (p.L397P), c.1265G>A (p.R422H), c.1264C>T (p.R422C), c.1306G>T (p.G436R), have not been reported before and in two others, the mutation corresponds to a recurrent missense mutation, c.790C>T (p.R264C), likely to be a hot spot of mutation. All together, it emerges that the TUBA1A related lissencephaly spectrum ranges from perisylvian pachygyria, in the less severe form, to posteriorly predominant pachygyria in the most severe, associated with dysgenesis of the anterior limb of the internal capsule and mild to severe cerebellar hypoplasia. When compared with a large series of lissencephaly of other origins (ILS17, ILSX or unknown origin), these features appear to be specific to TUBA1A related lissencephaly. In addition, TUBA1A mutated patients share a common clinical phenotype that consists of congenital microcephaly, mental retardation and diplegia/tetraplegia. CONCLUSIONS: Our data highlight the presence of consistent and specific abnormalities that should allow the differentiation of TUBA1A related lissencephalies from those related to LIS1, DCX and ARX genes.

Arthrogryposis in children: Etiological assessments and preparation of a protocol for etiological investigations.

INTRODUCTION: Arthrogryposis is a descriptive term defining a sign. It describes a set of joint contractures, sometimes identifiable in utero, present from birth and nonprogressive. This term includes a heterogeneous group of diseases, of neurological, neuromuscular, genetic or mechanical origin. The common physiopathological mechanism is fetal immobility syndrome. Two types of classification have been developed: a clinical one (types I, II and III) and an etiological one. The main aim of this study was to define a standardized protocol for etiological investigation based on a descriptive analysis of the various etiologies identified in a population of children followed up for arthrogryposis. Its secondary aim was to assess first the comprehensiveness and relevance of the complementary assessment and second the way in which the classifications proposed by Professor Judith Goslin Hall are applied. MATERIAL AND METHODS: Retrospective multicenter observational study. We enrolled pediatric patients with arthrogryposis being treated at a reference center for neuromuscular diseases, i.e., in three university hospital pediatric neurology units, between February 1997 and January 2017. RESULTS: Forty-two patients (25 boys and 17 girls) were enrolled. According to the clinical classification (Hall et al.), this population consisted of eight cases of type 1 arthrogryposis (19.1%), 14 type II (33.3%) and 20 type III (47.6%). The main etiology was neurological (19.1%), predominantly involving problems with gyration of a polymicrogyria type. Myopathic origin accounted for 9.5% of the population, predominantly involving genotyped distal arthrogryposis (ECEL1 gene). Additional tests produced a diagnosis of 25% type I, 43% type II and 75% type III. CONCLUSION: Arthrogryposis is a sign suggesting multiple etiologies. The main ones are neurological. Several genes have recently been identified, explaining the physiopathological mechanisms. The diagnostic process must be rigorous and coordinated within a multidisciplinary team, following a shared protocol for analysis.

[Non epileptic paroxysmal movement disorders in childhood]. / Mouvements anormaux paroxystiques non épileptiques de l'enfant.

Paroxysmal movement disorders are not uncommon in childhood, but are probably under-recognised. Paroxysmal movement disorders are a distinctive group of disorders that represents various clinical situations, characterised by intermittent and episodic disturbances of movement. Diagnosis relies on semiological analysis, mainly based on parental description of the manifestations; video recording (during an EEG-video monitoring or home made video) are often helpful to establish the correct diagnosis. In the large majority of the cases, paroxysmal movement disorders are benign situations. Some of them are transient, as they spontaneously stop over time (benign torticolis of infancy, paroxysmal tonic upgaze). Being familiar with these disorders will lead to accurate diagnosis, so avoiding useless investigations. Most of the time, no treatment will be required, and the families will be informed of the good prognosis.

[Bilateral facial nerve palsy associated with Epstein-Barr virus infection in a 3-year-old boy]. / Paralysie faciale bilatérale au cours d'une infection à virus d'Epstein­Barr.

Bilateral facial nerve palsy is a rare and sometimes difficult diagnosis. We describe a case of bilateral simultaneous facial nerve palsy associated with Epstein-Barr virus (EBV) infection in a 3-year-old boy. Several symptoms led to the diagnosis of EBV infection: the clinical situation (fever, stomachache, and throat infection), white blood cell count (5300/mm3 with 70% lymphocyte count), seroconversion with EBV-specific antibodies, lymphocytic meningitis, and a positive blood EBV polymerase chain reaction (9.3×103 copies of EBV-DNA). An MRI brain scan showed bilateral gadolinium enhancement of the facial nerve. A treatment plan with IV antibiotics (ceftriaxone) and corticosteroids was implemented. Antibiotics were stopped after the diagnosis of Lyme disease was ruled out. The patient's facial weakness improved within a few weeks. Bilateral facial nerve palsy is rare and, unlike unilateral facial palsy, it is idiopathic in only 20% of cases. Therefore, it requires further investigation and examination to search for the underlying etiology. Lyme disease is the first infectious disease that should be considered in children, especially in endemic areas. An antibiotic treatment effective against Borrelia burgdorferi should be set up until the diagnosis is negated or confirmed. Further examination should include a blood test (such as immunologic testing, and serologic testing for viruses and bacterium with neurological tropism), a cerebrospinal fluid test, and an MRI brain scan to exclude any serious or curable underlying etiology. Facial bilateral nerve palsy associated with EBV is rarely described in children. Neurological complications have been reported in 7% of all EBV infections. The facial nerve is the most frequently affected of all cranial nerves. Facial palsy described in EBV infections is bilateral in 35% of all cases. The physiopathology is currently unknown. Prognosis is good most of the time.

Effect of beta-dystroglycan processing on utrophin/Dp116 anchorage in normal and mdx mouse Schwann cell membrane.

In the peripheral nervous system, utrophin and the short dystrophin isoform (Dp116) are co-localized at the outermost layer of the myelin sheath of nerve fibers; together with the dystroglycan complex. Dp116 is associated with multiple glycoproteins, i.e. sarcoglycans, and alpha- and beta-dystroglycan, which anchor the cytoplasmic protein subcomplex to the extracellular basal lamina. In peripheral nerve, matrix metalloproteinase activity disrupts the dystroglycan complex by cleaving the extracellular domain of beta-dystroglycan. Metalloproteinase creates a 30 kDa fragment of beta-dystroglycan, leading to a disruption of the link between the extracellular matrix and the cell membrane. Here we asked if the processing of the beta-dystroglycan could influence the anchorage of Dp116 and/or utrophin in normal and mdx Schwann cell membrane. We showed that metalloproteinase-9 was more activated in mdx nerve than in wild-type ones. This activation leads to an accumulation of the 30 kDa beta-dystroglycan isoform and has an impact on the anchorage of Dp116 and utrophin isoforms in mdx Schwann cells membrane. Our results showed that Dp116 had greater affinity to the full length form of beta-dystroglycan than the 30 kDa form. Moreover, we showed for the first time that the short isoform of utrophin (Up71) was over-expressed in mdx Schwann cells compared with wild-type. In addition, this utrophin isoform (Up71) seems to have greater affinity to the 30 kDa beta-dystroglycan which could explain the increased stabilization of this 30 kDa form at the membrane compartment. Our results highlight the potential participation of the short utrophin isoform and the cleaved form of beta-dystroglycan in mdx Schwann cell membrane architecture. We proposed that these two proteins could be implicated in Schwann cell proliferation in response to a microenvironment stress such as mediated by accumulating macrophages in mdx mouse muscle inflammation sites.

[Congenital neuromuscular diseases with neonatal respiratory failure excluding myotonic dystrophy type 1 and infantile spinal muscular atrophy. Diagnosis strategy according to a 19-child series]. / Maladies neuromusculaires congénitales à expression respiratoire néonatale à l'exclusion de la dystrophie myotonique de type 1 et de l'amyotrophie spinale infantile. Stratégie d'exploration d'après une série de 19 enfants.

UNLABELLED: Apart from spinal muscular atrophy (SMA) and myotonic dystrophy type 1 (DM1), congenital neuromuscular diseases with early neonatal symptoms mean diagnostic and prognostic challenges mainly when infants require ventilatory support. OBJECTIVES: Consider a standardized strategy for infants suspected of congenital neuromuscular disease from analysis of the literature and retrospective experience with floppy and ventilatory support-dependent infants, after exclusion of well-known diseases (DM1, SMA). PATIENTS AND METHODS: Floppy infants requiring ventilatory support in their 1st month of life, but showing no evidence of DM1, SMA, Prader-Willi syndrome, or encephalopathy. The retrospective multicenter study was based on the response of regional referent neuropediatricians in the Reference Centre for Neuromuscular Diseases of Greater Southwest France to an inquiry about prenatal and perinatal history, investigations, diagnosis, and outcome of the child and family. It was conducted between 2007 and 2012. RESULTS: Among the 19 newborns studied, all had severe hypotonia. Prenatal and perinatal features were similar. Their outcome was generally severe: the median survival as measured by the Kaplan-Meier method was 6.9 months. Thirteen children died at a median age of 61 days; ten of them were treated with a palliative procedure. Five children had achieved respiratory independence but suffered from a small delay in motor development. Among the three children who continuously required ventilatory support, only one survived (follow-up period: 23 months); he was the only one undergoing tracheostomy in the cohort. Diagnostic processes were different, leading to pathological and genetic diagnosis for only six infants. There was only histological orientation for seven and no specific diagnostic orientation for the last six. These difficulties have led us to propose an exploration process based on the literature. CONCLUSION: This study highlights difficulties in obtaining a diagnosis and a precise prognosis for floppy ventilated infants. An exploration-standardized process for infants suspected of congenital neuromuscular diseases was made in order to standardize procedures. It could be used as a tool for all professionals involved.

[Parry-Romberg's syndrome and epilepsy]. / Syndrome de Parry-Romberg et épilepsie.

INTRODUCTION: Parry-Romberg's syndrome or progressive facial hemiatrophy is a rare disorder of unknown etiology which may be accompanied by neurological complications, frequently epilepsy, usually focal refractory epilepsy. The associated brain lesions are located on the same side as the half face atrophy and may progress. OBSERVATION: We report the cases of two patients with Parry-Romberg's syndrome and epilepsy. Neurosurgery was performed in one patient, enabling a histological study. CONCLUSION: The link between Parry-Romberg's syndrome and epilepsy is discussed and the neurodevelopmental theory with vascular dysgenesis is suggested.

[Genetics contribution to the understanding of autism]. / Apport de la génétique à la compréhension de l'autisme.

Autism is a pervasive developmental disorder characterised by an impairment in social interaction and in communication, with unusual behaviour. Genetic factors are predominent in autism pathogenesis, in contrast with the environmental factors that would modulate the phenotype. The genetic polymorphism and the phenotypic heterogeneity make the autism a complex disorder to study. Genetic research on families with multiple affected children and biochemical mechanisms studies represent the sources for identifying the susceptibility genes in autism.

[Trisomy 20 mosaicism revealed by pigmentary mosaicism of the Ito-type]. / Mosaïcisme pigmentaire de type Ito révélant une trisomie 20 en mosaïque.

INTRODUCTION: Ito hypomelanosis-type pigmentary mosaicism is characterized by congenital pigmentation disorders along Blaschko's lines. We report a case of Ito-type pigmentary mosaicism associated with a congenital growth hormone deficiency having revealed trisomy 20 mosaicism. OBSERVATION: A 4 year-old boy presented with congenital pigmentation disorders. His history was marked by: inter-uterine delayed growth of unknown etiology, a dysmorphic syndrome, psychomotor retardation with speech problems, right cryptorchidia and an isolated, idiopathic, congenital growth hormone deficiency that had been treated with recombinant somatropine since the age of three. The clinical examination revealed alternating hypo and hyper-pigmented maculae with linear distribution on the limbs and in "twirls" on the trunk following Blaschko's lines. The blood karyotype was normal, the karyotype on fibroblasts of hypopigmented skin revealed trisomy 20 mosaicism. DISCUSSION: The occurrence of pigmentary mosaicism related to trisomy 20 mosaicism is exceptional. The combination of Ito hypomelanosis-type pigmentary mosaicism and delayed growth due to growth hormone deficiency has never been reported before. Our observation, unusual because of such an association, raises the question of the eventual existence of associated genes located on the chromosome 20 implied in the secretion of growth hormone and/or melanogenesis. It also underlines the interest of conducting cytogenic explorations on fibroblasts of damaged skin in the case of Ito-type pigmentary mosaicism, even if the blood karyotype is normal or in the absence of a patent phenotype abnormality.

Expression patterns of dystrophin products, especially of apodystrophin-1/Dp71, in the neural retina of Amphibian urodele Pleurodeles waltl.

The expression patterns of the DMD (Duchenne Muscular Dystrophy) gene products, especially of Dp71 (apodystrophin-1) were investigated by immunofluorescence and immunoblotting in the retina of the Amphibian urodele Pleurodeles waltl. H-5A3 monoclonal antibody (mAb), directed against the C-terminal region of dystrophin/utrophin, and 5F3 mAb, directed against the last 31 amino acids of dystrophin and specific of Dp71, were used. Western blot analyses with H-5A3 mAb revealed distinct dystrophin-family isoforms in adult newt retinal extracts: a doublet 400-420 kDa, Dp260 isoform, a protein at about 120 kDa, and a diffuse zone at 70-80 kDa, which might correspond to Dp71. Reactivity with H-5A3 mAb appeared nearly restricted to the outer plexiform synaptic layer. On the other hand, Dp71-specific 5F3 mAb recognized trhee polypeptide bands at 70-80, 60-65 and 50-55 kDa in adult newt retina corresponding most probably to alternative spliced isoforms of Dp71. In immunohistochemistry by conventional epifluorescence microscopy, 5F3 labeling was mainly observed in the plexiform layers, the outer nuclear layer, and the photoreceptor inner segments, especially at the myoid regions. Analysis by confocal scanning laser microscopy (CSLM) revealed that 5F3 labeling was, in addition, present in the pigmented epithelium and the inner nuclear layer. Furthermore, CSLM showed that 5F3 staining at the myoids was concentrated at discrete domains underneath the plasma membrane. Our findings raised the question concerning the functional significance of Dp71 isoforms, especially at the myoid where Dp71 was detected for the first time, although it occurred here highly expressed. Putative role(s) played in this retinal compartment and other ones by Dp71 and/or other dystrophin isoforms were discussed.

[Central manifestations of dystrophinopathies]. / Manifestations centrales des dystrophinopathies.

The dystrophin gene involved in Duchenne and Becker muscular dystrophy is expressed in three main tissues resulting in clinical manifestations: skeletal muscle, heart and central nervous system. The 6 different existing dystrophins in the brain may play a role in the maturation and plasticity of neuronal synapses in particular by their functions in clustering and stabilization of different receptors at the post synaptic membrane. The possibility of an intellectual deficiency in Duchenne muscular dystrophy is known from the original description by Duchenne himself. Current data are in line with a constant cognitive impairment with a Gaussian curve shifted intellectual quotient (IQ) at -1 standard deviation from the standard population with an average IQ around 80. Clinical manifestations suggestive of a central nervous system involvement can affect all dystrophinopathies, including isolated central presentations without myopathic sign. The phenotypic spectrum appears broader and more subtle than non specific intellectual deficiency. The isolated or shared involvement of specific cognitive functions is possible (memory functions, executive functions, attention) with or without intellectual deficiency. Autism spectrum disorders are also among the encountered events. In clinical practice, it seems worth to ask for a measurement of serum creatine kinase (CK) in these different situations, keeping in mind that pure forms of central dystrophinopathies with a normal CK level have been recently reported.

Different utrophin and dystrophin properties related to their vascular smooth muscle distributions.

Monoclonal antibodies used to distinguish between dystrophin and utrophin were systematically applied to skeletal muscles containing arteries and veins. Small arteries were found to contain long forms of both utrophin and dystrophin, while small veins contained only long forms of utrophin. In addition, all sizes of vascular smooth muscles were demonstrated to contain another related Mr 80 kDa protein (possibly a short utrophin transcript). Regardless of their tissue distributions, we assumed that each of these molecules had distinct properties, i.e. dystrophin with a mechanical function and utrophin with an architectural function. This difference in the roles of dystrophin and utrophin could reduce the efficiency of protection against muscle membrane degeneration when utrophin overexpression is programmed.

Presence of long and short dystrophin and/or utrophin products in Torpedo marmorata peripheral nerves.

Peripheral nerves from rabbit and Torpedo marmorata were comparatively analyzed for the presence of short dystrophin products. Western blot analyses of Torpedo marmorata peripheral nerve extracts revealed the existence of three proteins belonging to the dystrophin family: a M(r) 400 kDa protein band detected with dystrophin/utrophin, dystrophin-specific and Torpedo utrophin-specific antibodies, a molecule identified as Dp116 and, for the first time at the protein level, a new protein probably corresponding to Up116. All of these products were carefully identified according to the specificities of the monoclonal antibodies used. In immunofluorescence studies, clear staining of the thin rim surrounding each Schwann cell-axon unit was observed in both Torpedo marmorata and rabbit peripheral nerves, showing colocalization of all of these molecules. Their potential functions were discussed in comparison to similar products found in rabbit peripheral nerves.

Congenital muscular dystrophy and cerebellar atrophy.

Two siblings and two other unrelated patients had congenital muscular weakness and dystrophic changes but normal immunocytochemical stainings for merosin, dystrophin, and dystrophin-related proteins on muscle biopsy. All had marked ataxia and cerebellar atrophy or hypoplasia. Cerebral white matter and cortical organization appeared normal.