Aharon Galil

PLA2G6 Mutation Underlies Infantile Neuroaxonal Dystrophy

Infantile neuroaxonal dystrophy (INAD) is an autosomal recessive progressive neurodegenerative disease that presents within the first 2 years of life and culminates in death by age 10 years. Affected individuals from two unrelated Bedouin Israeli kindreds were studied. Brain imaging demonstrated diffuse cerebellar atrophy and abnormal iron deposition in the medial and lateral globus pallidum. Progressive white-matter disease and reduction of the N-acetyl aspartate : chromium ratio were evident on magnetic resonance spectroscopy, suggesting loss of myelination. The clinical and radiological diagnosis of INAD was verified by sural nerve biopsy. The disease gene was mapped to a 1.17-Mb locus on chromosome 22q13.1 (LOD score 4.7 at recombination fraction 0 for SNP rs139897), and an underlying mutation common to both affected families was identified in PLA2G6, the gene encoding phospholipase A2 group VI (cytosolic, calcium-independent). These findings highlight a role of phospholipase in neurodegenerative disorders.

Compliance with home rehabilitation therapy by parents of children with disabilities in Jews and Bedouin in Israel

Among key points in making progress and succeeding with a therapeutic programme for children with disabilities is parental compliance with the regime for their child. The purpose of this study was to evaluate factors influencing compliance with home therapy in the Jewish and Bedouin populations. Data were collected by structured questionnaires. A total of 193 families participated (84% response rate) with children who ranged in age from 6 months to 6 years (mean age at first visit to the centre was 9.5 years in Jews and 16.1 years in Bedouin). Compliance was significantly lower among the Bedouin. Multivariate regression analysis showed that the strongest contributory factor in lack of compliance was being Bedouin. The second factor was intensity of questioning destiny, indicating that parents with these feelings may be less likely to comply with therapeutic regimes. Other factors which were associated with compliance were parents’education and socioeconomic status: lower levels on these dimensions corresponded with lower parental compliance. These results were illuminated by a trial intervention programme for Bedouin families which involved telephone contact, translation facilities, and detailed explanations during visits to the centre. Intervention increased the compliance rate of the Bedouin appointments with specialists to 76% (91 of 120 appointments) thereby reaching similar levels to those of the Jewish group. These preliminary results indicate that the strong association between non‐compliance and being Bedouin may be due to factors of communication, and that the Bedouin are receptive to therapeutic interventions when communicated in their own language.

COL11A2 mutation associated with autosomal recessive Weissenbacher–Zweymuller syndrome: Molecular and clinical overlap with otospondylomegaepiphyseal dysplasia (OSMED)†

Autosomal recessive Weissenbacher–Zweymuller syndrome (WZS) is a skeletal dysplasia characterized by rhizomelic dwarfism and severe hearing loss. Mutations in the COL11A2 gene have been implicated in causing the autosomal dominant form of this syndrome as well as non‐ocular Stickler syndrome and the autosomal recessive syndrome otospondylomegaepiphyseal dysplasia (OSMED). In a consanguineous Bedouin tribe living in Southern Israel, five individuals affected by autosomal recessive WZS were available for genetic analysis. Homozygosity of a mutation in the COL11A2 gene was found in all affected individuals. This finding lends molecular support to the clinical notion that autosomal recessive WZS and OSMED are a single entity.

The ocular manifestations of Weissenbacher-Zweymuller syndrome.

AbstractPurpose Weissenbacher–Zweymuller syndrome (WZS) is an autosomal recessive disorder of delayed skeletal maturation. Its characteristic features include rhizomelic dwarfism with metaphyseal and vertebral changes. It has been challenged whether WZS is a part of the spectrum of Stickler syndrome. We report ocular findings in the largest ever-presented series of patients with WZS.Methods Patients underwent a paediatric examination, including assessment of growth and development, genetic work-up and X-ray of vertebra and long bones. All had a complete ophthalmic examination, cycloplegic refraction, and face and body photography.Results All patients had hypertelorism and protruding eyes. Four patients had refractive errors necessitating optical correction ranging from +3 to –8 D. Two patients had strabismus. None had vitreoretinal degeneration, glaucoma, or cataract.Conclusions Ocular manifestations of WZS differ from those in Stickler syndrome, indicating that the two likely represent distinct clinical entities. Strabismus and various refractive errors often accompany WZS. An ophthalmologist should follow children with this disorder from an early age to prevent amblyopia.

Weissenbacher-Zweymuller syndrome: long-term follow-up of growth and psychomotor development.

A child with the distinguishing characteristics of Weissenbacher‐Zweymuller syndrome (WZS), a rare syndrome characterized by multiple skeletal and radiological abnormalities, dwarfism and developmental delays, was followed from birth to eight years. Follow‐up showed that the radiographic anomalies eventually disappeared, and that height, motor, cognitive and language development returned to normal by eight years of age. The childs normal development at school age supports the theory that WZS is a dysmaturational, rather than dysplastic, syndrome. Diagnosis of the syndrome at birth is essential to ensure proper management of the child and counselling for the parents.

Pediatricians' communication styles as correlates of global trust among Jewish and Bedouin parents of disabled children.

Objectives: There is a paucity of empirical studies of trust among parents of children with developmental disabilities. Trust is an important element in the patient-physician relationship, especially in medical rehabilitation, where continuous cooperation is essential for positive therapeutic outcomes. Trust is dependent on a variety of psychosocial factors, one of which is the physician’s communication style. The current study had three goals: (1) to compare two groups of Israeli parents, Jews and Bedouins, in terms of the levels of global trust in the pediatricians in a regional child development center; (2) to compare their perceptions of the pediatricians’ communication styles; and (3) to assess the association between three communication styles (caring, interest, and collaboration) and the parents’ trust in the pediatricians. Methods: The sample included 193 parents of disabled children ranging from 6 months to 6 years of age. Global trust and parents’ perceptions concerning their communication with the center’s pediatricians were measured by scales developed for this research. Results: Despite the large cultural differences that exist between the Jewish and Bedouin groups, the only significant difference between them was that Jewish parents’ reported a significantly higher level of collaboration compared with the Bedouins. Global trust in the pediatrician was significantly predicted by the interest and collaboration communication styles, but ethnicity was not a significant predictor. Conclusion: These findings underscore the importance of physicians’ interpersonal competence and skills in the therapeutic relationship and support the increasing trend of including doctor-patient communication training in undergraduate and continuing medical education.

Trends in adolescent sexual risk behaviors.

Many societies worldwide are faced with an increase in adolescent pregnancy, rape, sexual abuse and sexually transmitted disease due to different sexual behaviors and sometimes lack of responsible sexual behaviors. The World Health Organization and the Surgeon General of the United States Government have called for action to this serious public health issue. In this short communication data from the United States, Canada and Israel is presented with a call for a professional response to this public health challenge.

A syndrome of congenital microcephaly, intellectual disability and dysmorphism with a homozygous mutation in FRMD4A

A consanguineous Bedouin Israeli kindred presented with a novel autosomal recessive intellectual disability syndrome of congenital microcephaly, low anterior hairline, bitemporal narrowing, low-set protruding ears, strabismus and tented thick eyebrows with sparse hair in their medial segment. Brain imaging demonstrated various degrees of agenesis of corpus callosum and hypoplasia of the vermis and cerebellum. Genome-wide linkage analysis followed by fine mapping defined a 7.67 Mb disease-associated locus (LOD score 4.99 at θ=0 for marker D10S1653). Sequencing of the 48 genes within the locus identified a single non-synonymous homozygous duplication frameshift mutation of 13 nucleotides (c.2134_2146dup13) within the coding region of FRMD4A, that was common to all affected individuals and not found in 180 non-related Bedouin controls. Three of 50 remotely related healthy controls of the same tribe were heterozygous for the mutation. FRMD4A, member of the FERM superfamily, is involved in cell structure, transport and signaling. It regulates cell polarity by playing an important role in the activation of ARF6, mediating the interaction between Par3 and the ARF6 guanine nucleotide exchange factor. ARF6 is known to modulate cell polarity in neurons, and regulates dendritic branching in hippocampal neurons and neurite outgrowth. The FRMD4 domain that is essential for determining cell polarity through interaction with Par3 is truncated by the c.2134_2146dup13 mutation. FRMD4A polymorphisms were recently suggested to be a risk factor for Alzheimer’s disease. We now show a homozygous frameshift mutation of the same gene in a severe neurologic syndrome with unique dysmorphism.

Comparison of a commercial ELISA kit and a neutralization assay for assessment of humoral immunity to measles virus

Abstract Efficient control of measles apparently requires reimmunization of susceptibles. The classic techniques used for estimation of measles susceptibility, neutralization and hemeagglutination inhibition, are neither convenient nor exactly comparable when carried out in different laboratories. We have compared a one-dilution commercial enzyme-linked immunosorbant assay (ELISA) to a classic neutralization test with respect to its ability to designate susceptibles as well as its ability to indicate post-reimmunization rises in measles antibody levels. A group of controls not deemed to require reimmunization was tested in parallel. The results indicate that the simple and standardized commercial assay may be able to substitute for the classic assays, which can only be carried out in specialized laboratories, when simple screening for persons with low levels of antibodies to measles or when evaluations of responses to (re)immunizations are required.

Detection of rotavirus specific antibodies in saliva

We have previously demonstrated production of secretory antibodies against a systemic pathogen, measles virus [1]. With many oral vaccines now being tested, a simple and efficient method for determination of immunity to mucosal pathogens is needed, especially for very small children. Since the antibody response in saliva may reflect stimulation of the mucosal immune system by antigen presentation in the Peyer’s patches, and since saliva is easily obtained even from infants, we wished to determine whether the presence of salivary antibodies may be indicative of protective immunity in rotavirus infections.