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Biomedical subjects

M Shohat

Publications and source records attributed to M Shohat.

At least 109 records · Page 6Linked to original sources
PubMed1994

Desbuquois syndrome: clinical, radiographic, and morphologic characterization.

To further characterize the clinical, radiographic and chondro-osseous morphologic changes in the Desbuquois syndrome, 7 patients from three sibships are described. They all had prenatal onset severe rhizomelic and mesomelic shortness with marked joint laxity and marked micrognathia. Radiographic changes were distinct, consisting of a supernumerary ossification center between the proximal phalanx of the index finger and the second metacarpal, and variable thumb changes. The femoral necks showed enlargement of the lesser trochanter with metaphyseal breaking, producing a characteristic "monkey wrench" (Swedish key) appearance. Growth plate cartilage showed dilated cisterns of rough endoplasmic reticulum in reserve zone chondrocytes. Three of the 7 cases were diagnosed prenatally by second trimester ultrasound and one case by fetoscopy. This syndrome exhibits significant phenotypic variability and must be differentiated from the Catel-Manzke syndrome which exhibits similar radiographic changes in the hands.

Adolescent↗
PubMed1994

Involvement of 11p15 and 3q21q26 in therapy-related myeloid leukemia (t-ML) in children. Case reports and review of the literature.

The cytogenetic findings of therapy-related myeloid leukemia (t-ML) in three children are presented. These included one male patient with acute lymphoblastic leukemia (ALL) who underwent bone marrow transplantation and developed therapy-related myeloproliferative disease (t-MPD) in the female-donor hematopoietic cells 2.5 years after receiving radiation and epipodophyllotoxin therapy for ALL testicular relapse. Bone marrow leukemic cell karyotype revealed 46,XX,add (11)(p15) and a normal female karyotype in the peripheral blood lymphocytes. The other two children, one with ALL and one with ganglioneuroblastoma, developed fatal t-MPD and therapy-related acute myeloblastic leukemia (t-AML) preceded by myelodysplastic syndrome (t-MDS), respectively, 5 years after diagnosis, following administration of alkylating agents and irradiation. Monosomy 7 was present in both, and was combined with inv(3)(q21q26) in the second patient. Our review of the cytogenetic findings in 91 previously reported pediatric patients with t-ML suggested that the involvement of 11p15 and 3q21-->23, 3q24-q26 with or without a combination of translocation 11q23 and -7/7q-, respectively, are nonrandom aberrations of t-ML in children. Comparison of the chromosomal changes in t-ML between the pediatric and an adult series revealed some differences which may result from differences in treatment modalities and which, in addition, may indicate a possible role of genetic and/or age-dependent factors in the pathogenesis of therapy-related leukemogenesis in children.

Antineoplastic Agents↗
PubMed1994

Consanguineous matings in an Israeli-Arab community.

OBJECTIVE: To determine the frequency of consanguineous marriages and the inbreeding coefficient in Israeli Arabs. DESIGN: Cohort survey. SETTING: General community in 70 settlements in Israel. PARTICIPANTS: Nine thousand three hundred Israeli-Arab students in the second grade were sent questionnaires to be filled out by their fathers, with 8521 completed questionnaires returned. INTERVENTIONS: None. MEASUREMENTS/MAIN RESULTS: Of the 8521 completed questionnaires, 1156 (14%) were from urban areas, 2267 (27%) were from suburban areas, and 5098 (60%) were from rural areas. The prevalence of consanguineous matings in the studied group was 44.3%, with a mean inbreeding coefficient of .0192. This prevalence is high and was highest in the rural areas. Marriages between first cousins occurred more often than marriages between other relatives in all locations. CONCLUSION: The frequency of consanguineous marriages is quite high among Israeli Arabs, approaching 50%.

Consanguinity↗
PubMed1994

Prenatal diagnosis of twin zygosity by DNA 'fingerprint' analysis.

A twin pregnancy with one hydrocephalic fetus with oligohydramnios is presented. Sonographic evaluation could not exclude monochorionicity. Before considering selective feticide, blood samples from both fetuses were examined for DNA 'fingerprint' analysis. The different banding patterns of the blood samples established dizygosity. This procedure is suggested in cases where sonography fails to determine chorionicity.

Abortion, Therapeutic↗
PubMed1994

High incidence of central nervous system malformations associated with marked parental consanguinity in an Israeli Arab community.

It is common among Israeli Arabs who live in villages to prefer consanguineous marriages, particularly among first cousins. In addition, such villages are populated by a few (< 20) original families, and inter-family/inter-village marriages are infrequent. The purpose of this study was to examine the incidence of congenital malformation of the central nervous system associated with such "consanguinity" in Taibe, a large Arab village, 30 km from Tel Aviv. Six hundred and ten families were prospectively ascertained through infants who were routinely seen in the local "Well Baby Clinics". A significant increase in the incidence of major malformations was noted in relation to the closeness of the parental relationship. For the index cases group, the prevalence of individuals with major malformations was 5.8% in the product of inter-village marriages, 8.3% in the intra-village non-related matings, 15.1% in the distant consanguineous group, and up to 15.8% in the progeny of first-cousin marriages (P < 0.001). Malformations of the central nervous system consisted of 1/3 to 1/2 of the total malformations in the consanguineous group versus less than 1/5 in the non-consanguineous groups. The study demonstrates a marked high rate of consanguineous marriages, the effect of which leads to a marked increase in major malformations and especially those of the central nervous system. This requires a unique genetic counseling approach.

Adult↗
PubMed1994

Localization of the gene for Darier disease to a 5-cM interval on chromosome 12q.

Darier disease is an autosomal dominant abnormality of epidermal differentiation characterized clinically by the presence of hyperkeratotic papules on the skin and histologically by the loss of cell cohesion and by disorderly keratinization. Two groups recently found evidence that the gene whose mutations underlie this disease is located at chromosome 12q23-q24.1, a site on chromosome 12 that clearly is distal to the type II keratin gene cluster. We report here evidence for sublocalization to a 5-cM region of that site in an additional ten families of European and Middle Eastern ancestry with a combined lod score in excess of 20.

Adult↗
PubMed1994

Myotonic dystrophy gene analysis in affected Israeli families.

Myotonic dystrophy (DM) is an autosomal dominant disease with an estimated incidence of 1:7,500 individuals. The clinical manifestations are variable and include muscle wasting and weakness, myotonia, intellectual impairment, cardiac abnormalities, cataracts, and testicular atrophy. Despite its phenotypic variability, the disease is genetically homogeneous, and a specific molecular defect has been located to chromosome 19q13.3 and found to be associated with the expansion and instability of trinucleotide (CTG) repeats. Whereas normal individuals have 5-36 CTG repeats, affected individuals have 50 to several thousands. Therefore, DM can now be diagnosed accurately using molecular biology techniques that allow detailed analysis and determination of the size of DNA in the unstable DM gene region. In this way even mildly affected patients can be identified. We used this method to study the DM gene in 11 affected Israeli families (39 individuals). In most of the families, the unstable DNA sequence increased in size when transmitted to offspring. In one of the families we found contraction of the CTG repeat in a DM offspring of an affected male; and in another family a CTG repeat contraction occurred in three offspring of an affected female while in the fourth offspring there was CTG expansion. Southern blot analysis using BglI restriction provided the most accurate technical results. There was an obvious phenotype/genotype correlation between the size of the CTG repeat and severity of disease.

Adolescent↗
PubMed1994

Further mapping of the properdin deficiency gene in a Tunisian Jewish family--evidence for genetic homogeneity.

The properdin deficiency gene has been localized to Xp21.1-Xcen; however, it is not clear whether the mutation responsible for the disease co-maps exactly with the structural properdin gene. Based on a recent study on a total of six families, the gene was found linked to DXS255 (theta = 0.00). As only a few families have been studied, it is not known whether the same gene is responsible for the disease in all families. In order to better localize the disease gene in Israel, we studied a Tunisian Jewish family with properdin deficiency for linkage with various X-markers. A maximum lod score of 1.93 at theta = 0.00 was calculated with the DXS7 probe while there was one recombination with DXS255. This study helps to better localize the properdin deficiency gene to Xp11.3-p21.1 proximal to DXS255 locus and confirms that there is no indication of genetic heterogeneity. Whether the properdin structural gene (PFC) and properdin deficiency locus are one and the same await demonstration of mutations in the structural gene in patients with properdin deficiency.

Chromosome Mapping↗
PubMed1993

Regional mapping of the gene for familial Mediterranean fever on human chromosome 16p13.

Familial Mediterranean fever (FMF) is an autosomal recessively inherited inflammatory disorder characterized by recurrent short episodes of fever, peritonitis, arthritis, and pleuritis. Recently, linkage was demonstrated between FMF and the VNTR probes 3'HVR and 5'HVR of the alpha-globin complex at 16p13.3 (theta = 0.06-0.10, Lodmax = 9.76-14.47) and the insertion/deletion polymorphism detected by the probe CMM65 of D16S84 (theta = 0.04, Lodmax = 9.17). We have now mapped the FMF gene between the two flanking markers D16S283/D16S291 (theta = 0.038) and D16S80 (theta = 0.159). The proximity of the microsatellite markers in D16S283 and D16S291 to the FMF gene allows preclinical diagnosis in most pedigrees with affected individuals.

Chromosomes, Human, Pair 16↗
PubMed1993

New form of spondyloepimetaphyseal dysplasia (SEMD) in Jewish family of Iraqi origin.

We report a distinct type of spondyloepimetaphyseal dysplasia seen in 2 sibs and their second cousin, characterized by early onset severe short stature, small chest, and distended abdomen. They had short neck, severe lumbar lordosis, and marked genu varum due to fibular overgrowth and joint laxity. Radiographically, the patients had platyspondyly, initially noted during the first years of life, with central hypoplasia of the vertebral bodies. At a later age, the vertebrae appear squared with mild interpedicular narrowing. The long bone changes, which at early age resemble those seen in achondroplasia, later include general metaphyseal irregularities and significant epiphyseal ossification delay. These patients present a previously undescribed form of spondyloepimetaphyseal dysplasia, most probably transmitted as an autosomal recessive tract.

Child↗
PubMed1993

Hearing loss and temporal bone structure in achondroplasia.

Characteristic temporal bone changes have recently been defined by high resolution CT in nine patients with achondroplasia (Cobb et al., Am J Neuroradiol 9:1195, 1988). These included narrowing of the skull base and "towering" petrous ridges resulting in abnormal orientation of the inner and middle ear structures. In order to determine whether these morphologic changes are the cause of the hearing deficit in achondroplasia, audiometric studies and ENT evaluation were performed in eight of the nine patients. All had a history of frequent otitis media and four had experienced tympanic membrane tube insertion. Three patients had significant sensorineural hearing loss, two had conductive hearing loss and one patient had combined hearing loss. None of the temporal bone morphologic changes were found to be correlated with the degree of either sensorineural or conductive hearing loss. Fusion of the ossicular chain was not present in any of our cases. Appropriate treatment of frequent acute otitis media and early awareness of middle ear effusions and conductive hearing loss in children with achondroplasia may be of great importance in preventing permanent hearing loss.

Achondroplasia↗
PubMed1993

New epiphyseal stippling syndrome with osteoclastic hyperplasia.

We present a lethal skeletal dysplasia characterized radiographically by severe stippling of the lower spine and long bones and periosteal cloaking. In contrast to the normal morphology of the epiphyses and growth plates, the marrow was filled with loose fibrous tissue containing numerous large multinucleated osteoclasts which were associated with Howship's lacunae on the endosteal surface. We suggest the term "Pacman dysplasia" to describe this unusual histologic change that characterizes this new bone dysplasia.

Chondrodysplasia Punctata↗
PubMed1993

A form of sensorineural deafness is determined by a mitochondrial and an autosomal locus: evidence from pedigree segregation analysis.

We have previously reported a large Israeli-Arab pedigree with sensorineural deafness possibly determined simultaneously by two loci--one mitochondrial, and one autosomal recessive. This was analyzed by extending classic segregation analysis methods to the many nuclear families derived from the maternal line pedigree. Here we expand this pedigree and extend our analysis by using the regressive models for segregation analysis on the entire pedigree. The corresponding REGD computer program was utilized and the marrying-in males' and paternal line members' affection statuses were assigned as unknown to accommodate the exclusive maternal transmission pattern. For the autosomal locus, a simple autosomal recessive (q = 0.52) model with a nearly complete penetrance (0.93) was found to be the best-fitting model. Equally importantly, we were also able to use the power of the regressive models to test the hypothesis of mitochondrial heteroplasmy as an alternative for the proposed autosomal locus. We found no evidence for the heteroplasmy hypothesis as an explanation for the incomplete maternal transmission of deafness in this pedigree. Thus, even if the mitochondrial mutation occurred in a heteroplasmic distribution in the family members, this could not explain the familial aggregation in this pedigree, and an autosomal recessive locus is still required. These results provide further support for the concept that the sensorineural deafness occurring in this large Israeli-Arab pedigree results from simultaneous involvement of two genes at two different loci, one mitochondrial and likely homoplasmic, and the other autosomal and recessive.

Computer Simulation↗
PubMed1993

Soluble interleukin-2 receptor and interleukin-2 in human amniotic fluid of normal and abnormal pregnancies.

In the present study, 63 specimens of human amniotic fluid were tested for the presence of free soluble interleukin-2 receptor (IL-2R). Thirty-two of these were also tested for the presence of IL-2. Significant reduction in free soluble IL-2R (IU/ml) or free IL-2R (IU/mg albumin) levels were found in the amniotic fluid obtained from pregnant women with Down's syndrome fetuses as compared with normal pregnancies. In addition normal amniotic fluid was found to contain low levels of IL-2, while no IL-2 was found in amniotic fluid from pregnant women with Down's syndrome fetuses when tested by two different tests.

Amniotic Fluid↗