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F Greenberg

Publications and source records attributed to F Greenberg.

At least 19 recordsLinked to original sources
PubMed1997

The Pointer syndrome: a new syndrome with skeletal abnormalities, camptodactyly, facial anomalies, and feeding difficulties.

We describe a brother and sister with a unique combination of skeletal findings including camptodactyly (phalangeal dislocations), facial anomalies, neonatal respiratory problems, and feeding problems due to poor suck. Metaphyseal splaying, osteopenia, endosteal bone apposition, campomelia, and multiple fractures characterize the other skeletal abnormalities. The parents are first cousins once removed and are unaffected. These cases appear to represent a previously undescribed autosomal recessive disorder.

Abnormalities, Multiple↗
PubMed1997

Chromosome 1p36 deletions: the clinical phenotype and molecular characterization of a common newly delineated syndrome.

Deletions of the distal short arm of chromosome 1 (1p36) represent a common, newly delineated deletion syndrome, characterized by moderate to severe psychomotor retardation, seizures, growth delay, and dysmorphic features. Previous cytogenetic underascertainment of this chromosomal deletion has made it difficult to characterize the clinical and molecular aspects of the syndrome. Recent advances in cytogenetic technology, particularly FISH, have greatly improved the ability to identify 1p36 deletions and have allowed a clearer definition of the clinical phenotype and molecular characteristics of this syndrome. We have identified 14 patients with chromosome 1p36 deletions and have assessed the frequency of each phenotypic feature and clinical manifestation in the 13 patients with pure 1p36 deletions. The physical extent and parental origin of each deletion were determined by use of FISH probes on cytogenetic preparations and by analysis of polymorphic DNA markers in the patients and their available parents. Clinical examinations revealed that the most common features and medical problems in patients with this deletion syndrome include large anterior fontanelle (100%), motor delay/hypotonia (92%), moderate to severe mental retardation (92%), growth delay (85%), pointed chin (80%), eye/vision problems (75%), seizures (72%), flat nasal bridge (65%), clinodactyly and/or short fifth finger(s) (64%), low-set ear(s) (59%), ear asymmetry (57%), hearing deficits (56%), abusive behavior (56%), thickened ear helices (53%), and deep-set eyes (50%). FISH and DNA polymorphism analysis showed that there is no uniform region of deletion but, rather, a spectrum of different deletion sizes with a common minimal region of deletion overlap.

Abnormalities, Multiple↗
PubMed1996

Multi-disciplinary clinical study of Smith-Magenis syndrome (deletion 17p11.2)

Smith-Magenis syndrome (SMS) is a multiple congenital anomaly, mental retardation (MCA/MR) syndrome associated with deletion of chromosome 17 band p11.2. As part of a multi-disciplinary clinical, cytogenetic, and molecular approach to SMS, detailed clinical studies including radiographic, neurologic, developmental, ophthalmologic, otolaryngologic, and audiologic evaluations were performed on 27 SMS patients. Significant findings include otolaryngologic abnormalities in 94%, eye abnormalities in 85%, sleep abnormalities (especially reduced REM sleep) in 75%, hearing impairment in 68% (approximately 65% conductive and 35% sensorineural), scoliosis in 65%, brain abnormalities (predominantly ventriculomegaly) in 52%, cardiac abnormalities in at least 37%, renal anomalies (especially duplication of the collecting system) in 35%, low thyroxine levels in 29%, low immunoglobulin levels in 23%, and forearm abnormalities in 16%. The measured IQ ranged between 20-78, most patients falling in the moderate range of mental retardation at 40-54, although several patients scored in the mild or borderline range. The frequency of these many abnormalities in SMS suggests that patients should be evaluated thoroughly for associated complications both at the time of diagnosis and at least annually thereafter.

Abnormalities, Multiple↗
PubMed1996

Hispanic origin and neural tube defects in Houston/Harris County, Texas. I. Descriptive epidemiology.

High prevalences of anencephaly and neural tube defects (NTDs) have recently been recorded for several Texas counties bordering Mexico. In addition, a few investigators have reported Hispanics to be at elevated risk for NTDs (anencephaly and spina bifida). Factors contributing to this risk have not been established. The authors conducted a study of NTDs in Harris County, Texas, to determine the prevalence of each defect. Prevalence was established by identifying cases among resident live births and fetal deaths (stillbirths at > or = 20 weeks) occurring from April 1, 1989, through December 31, 1991. Using multiple case ascertainment methods, 59 cases of anencephaly and 32 cases of spina bifida were detected, resulting in prevalences of 3.8 (95% confidence interval 2.9-4.9) and 2.0 (95% confidence interval 1.4-2.8) per 10,000 live births, respectively. The ratio of anencephaly prevalence to spina bifida prevalence was 2:1 in 1989, 1:1 in 1990, and 3:1 in 1991, with a significant difference in 1991. The female:male prevalence ratio was 1.0 for spina bifida and 2.2 for anencephaly, and was higher still for anencephaly among non-Hispanics (prevalence ratio = 5.6). For each defect, Hispanics experienced a prevalence approximately three times that of non-Hispanics. This ethnic difference was greater for males with anencephaly and for females with spina bifida. For anencephaly, the Hispanic:white/Anglo prevalence ratio (4.2) and the African-American:white/Anglo prevalence ratio (1.9) were greatly elevated and the Hispanic:African-American prevalence ratio (2.2) was similar, relative to comparable studies from the past two decades. The prevalence of anencephaly recorded for public hospitals (7.0 per 10,000) was three times greater than that for private hospitals (2.4 per 10,000). Spina bifida figures were similar for public (prevalence = 2.2 per 10,000) and private (prevalence = 2.0 per 10,000) hospitals. A significantly higher prevalence of both defects was documented among Hispanics in Harris County. The higher anencephaly rates among Hispanics, African-Americans, and those using public hospitals in an era of NTD screening, prenatal diagnosis, and elective pregnancy termination suggest that socioeconomic and perhaps cultural/religious factors might influence the recorded birth prevalence of this defect in particular groups.

Anencephaly↗
PubMed1996

Hispanic origin and neural tube defects in Houston/Harris County, Texas. II. Risk factors.

Several investigators have reported Hispanics to be at elevated risk for neural tube defects (anencephaly and spina bifida). Factors contributing to this risk have not been established. The authors conducted a case-control study of neural tube defects (NTDs) among births occurring in Harris County, Texas, from April 1, 1989, through December 31, 1991. Through the use of multiple ascertainment methods, 59 cases of anencephaly and 32 cases of spina bifida were detected. Controls (n = 451) were sampled for the same time period from Harris County vital records. Regardless of how Hispanic ethnicity was classified, having a Hispanic parent was a risk factor for both anencepahly and spina bifida. The primary etiologic question was whether increased NTD risk in Hispanics is explained by maternal diabetes or by other factors (e.g., maternal birthplace, prenatal care, reproductive history, age, socioeconomic status). Mexico-born Hispanics were no more likely than Texas-born Hispanics to deliver a fetus or infant with an NTD. Having a Hispanic mother was a risk factor for anencephaly among infants born to women with early prenatal care (odds ratio (OR) = 4.54, 95% confidence interval (CI) 2.21-9.40) but not for those born to latecomers. Earlier prenatal care seemed "protective" for non-Hispanics (OR = 0.18, 95% CI 0.06-0.65) but not for Hispanics. After simultaneous adjustment for eight variables in multivariate analysis, having a Hispanic (versus non-Hispanic) mother remained a strong risk factor for both anencephaly (OR = 2.58, 95% CI 1.19-5.61) and spina bifida (OR = 3.71, 95% CI 1.48-9.31). Any previous pregnancy termination/fetal loss was also associated with anencephaly in a final logistic regression model (OR = 2.48, 95% CI 1.20-5.10), and having a teenage mother (aged < 20 years) approached significance (OR = 2.21, 95% CI 0.92-5.31). "Hispanic mother" was the only study variable significantly associated with spina bifida in multivariate analysis. Results for diabetes suggested no association with anencephaly (OR = 1.24, 95% CI 0.25-6.17). An increased risk of NTDs among Hispanics remained after controlling for other factors. For anencephaly, this risk might be partially explained by economic and cultural differences between Hispanics and non-Hispanics, and the effect of these factors on rates of prenatal diagnosis and elective pregnancy termination.

Adult↗
PubMed1996

A clinical and molecular study of mosaicism for trisomy 17.

Trisomy 17 has never been reported in a live birth. We present a case of mosaic trisomy 17 in a male presenting with mental retardation, seizures, attention deficit hyperactivity and autistic disorders, hearing loss, growth retardation, microcephaly, and minor anomalies. Although peripheral blood lymphocyte chromosomes were normal, trisomy 17 was present in the skin fibroblasts. The percentage of abnormal cells appears to have increased from 18% in an initial skin biopsy at age 3 years 8 months to 80% at age 8 years 8 months. Molecular analysis using 13 highly polymorphic markers spanning the length of chromosome 17 demonstrated the extra chromosome 17 in the skin to be of paternal origin. Three alleles were never seen in the trisomic cell line, suggesting that the extra chromosome arose through a mitotic duplication error after conception. Uniparental disomy was excluded in the euploid blood sample. Although Smith-Magenis syndrome involves a deletion of proximal 17p, some of the clinical features of this mosaic trisomy 17 patient, such as decreased REM sleep and increased tolerance to pain, are suggestive of phenotypic features observed in Smith-Magenis syndrome. We speculate that there are dosage-sensitive genes located in 17p11.2 that produce these phenotypes for either deficiencies or over-expression of their gene products.

Abnormalities, Multiple↗
PubMed1996

Quantification by flow cytometry of chromosome-17 deletions in Smith-Magenis syndrome patients.

We have used bivariate flow karyotyping to quantify the deletions involving chromosome 17 in sixteen patients with Smith-Magenis syndrome (SMS). The fluorescence intensities of mitotic chromosomes stained with Hoechst 33258 and chromomycin were quantified in a dual-beam flow cytometer. For each patient, the position of the peak representing the deleted chromosome 17 was compared to those of the normal homologs of an unaffected parent. The patients could be classified into four groups based on the size of their deletions. The deletions ranged from approximately 9-10 Mb (approximately 10-11% of the chromosome) to below the detection limit of the technique (2 Mb). Different deletion sizes were detected among patients whose high-resolution banding results were similar. Some deletions detected by banding were not detected by flow analyses. Deletion estimates are largely consistent with the results of molecular analyses. Patients with larger deletions that extend into band 17p 12 have abnormal electrophysiologic studies of peripheral nerves. Deletion size does not appear to correlate with the degree of mental retardation, presence of behavioral abnormalities, craniofacial anomalies or common skeletal findings in SMS. By identifying patients with varying deletion sizes, these data will aid the construction of a long-range deletion-based map of 17p11.2 and identification of the genes involved in this syndrome.

Abnormalities, Multiple↗
PubMed1996

Ophthalmic manifestations of Smith-Magenis syndrome.

PURPOSE: The Smith-Magenis syndrome (SMS) is a multiple-anomaly, mental retardation syndrome associated with deletions of a contiguous region of chromosome 17p11.2. Prior reports have described ophthalmic anomalies with SMS, including telecanthus, ptosis, strabismus, myopia, iris anomalies, cataracts, optic nerve hypoplasia, and retinal detachment. This report defines the ophthalmic spectrum in 28 individuals with SMS subjected to a multidisciplinary clinical and molecular survey. METHODS: Individuals with deletion of chromosome 17p11.2 detected by high-resolution cytogenetic analysis underwent complete ophthalmologic evaluation comprised of ophthalmic history, visual acuity, cycloplegic refraction, motility, and biomicroscopic and ophthalmoscopic examination. RESULTS: Among the 28 subjects, ranging in age from 0.8 to 29.3 years, the most frequent ocular findings were iris anomalies (68%), microcornea (50%), myopia (42%), and strabismus (32%). Bilateral microphthalmos with uveal and retinal coloboma was observed in one individual. No subject had cataract or retinal detachment. CONCLUSIONS: This is the largest single-center series of subjects with SMS that includes ophthalmic evaluation. As in prior reports, iris anomalies and strabismus were observed, but microcornea had not been noted previously. The absolute refractive error was hypermetropic in half of these subjects. Cataract, ptosis, and retinal pathology, including detachment, were not observed in any subject. All individuals with SMS should be evaluated by an ophthalmologist, with special attention to strabismus, microcornea, iris anomalies, and refractive errors.

Abnormalities, Multiple↗
PubMed1996

Molecular analyses of 17p11.2 deletions in 62 Smith-Magenis syndrome patients.

Smith-Magenis syndrome (SMS) is a clinically recognizable, multiple congenital anomalies/mental retardation syndrome caused by an interstitial deletion involving band p11.2 of chromosome 17. Toward the molecular definition of the interval defining this microdeletion syndrome, 62 unrelated SMS patients in conjunction with 70 available unaffected parents were molecularly analyzed with respect to the presence or absence of 14 loci in the proximal region of the short arm of chromosome 17. A multifaceted approach was used to determine deletion status at the various loci that combined (i) FISH analysis, (ii)PCR and Southern analysis of somatic cell hybrids retaining the deleted chromosome 17 from selected patients, and (iii) genotype determination of patients for whom a parent(s) was available at four microsatellite marker loci and at four loci with associated RFLPs. The relative order of two novel anonymous markers and a new microsatellite marker was determined in 17p11.2. The results confirmed that the proximal deletion breakpoint in the majority of SMS patients is located between markers D17S58 (EW301) and D17S446 (FG1) within the 17p11.1-17p11.2 region. The common distal breakpoint was mapped between markers cCI17-638, which lies distal to D17S71, and cCI17-498, which lies proximal to the Charcot Marie-Tooth disease type 1A locus. The locus D17S258 was found to be deleted in all 62 patients, and probes from this region can be used for diagnosis of the SMS deletion by FISH. Ten patients demonstrated molecularly distinct deletions; of these, two patients had smaller deletions and will enable the definition of the critical interval for SMS.

Abnormalities, Multiple↗
PubMed1996

Duplication of the PMP22 gene in 17p partial trisomy patients with Charcot-Marie-Tooth type-1 neuropathy.

Autosomal dominant Charcot-Marie-Tooth type-1A neuropathy (CMT1A) is a demyelinating peripheral nerve disorder that is commonly associated with a submicroscopic tandem DNA duplication of a 1.5-Mb region of 17p11.2p12 that contains the peripheral myelin gene PMP22. Clinical features of CMT1A include progressive distal muscle atrophy and weakness, foot and hand deformities, gait abnormalities, absent reflexes, and the completely penetrant electrophysiologic phenotype of symmetric reductions in motor nerve conduction velocities (NCVs). Molecular and fluorescense in situ hybridization (FISH) analyses were performed to determine the duplication status of the PMP22 gene in four patients with rare cytogenetic duplications of 17p. Neuropathologic features of CMT1A were seen in two of these four patients, in addition to the complex phenotype asociated with 17p partial trisomy. Our findings show that the CMT1A phenotype of reduced NCV is specifically associated with PMP22 gene duplications, thus providing further support for the PMP22 gene dosage mechanism for CMT1A.

Blotting, Southern↗
PubMed1995

Smith-Magenis syndrome deletion: a case with equivocal cytogenetic findings resolved by fluorescence in situ hybridization.

The availability of markers for the 17p11.2 region has enabled the diagnosis of Smith-Magenis syndrome (SMS) by fluorescence in situ hybridization (FISH). SMS is typically associated with a discernible deletion of band 17p11.2 upon cytogenetic analysis at a resolution of 400-550 bands. We present a case that illustrates the importance of using FISH to confirm a cytogenetic diagnosis of del(17)(p11.2). Four independent cytogenetic analyses were performed with different conclusions. Results of low resolution analyses of amniocytes and peripheral blood lymphocytes were apparently normal, while high resolution analyses of peripheral blood samples in two laboratories indicated mosaicism for del(17)(p11.2). FISH clearly demonstrated a 17p deletion on one chromosome of all peripheral blood cells analyzed and ruled out mosaicism unambiguously. The deletion was undetectable by flow cytometric quantitation of chromosomal DNA content, suggesting that it is less than 2 Mb. We conclude that FISH should be used to detect the SMS deletion when routine chromosome analysis fails to detect it and to verify mosaicism.

Chromosome Aberrations↗
PubMed1995

Replication banding and molecular studies of a mosaic, unbalanced dic(X;15)(Xpter-->Xq26.1::15p11-->15qter).

We present a patient with a chromosomal mosaicism involving the X chromosome. One cell line is 45,X and the other has a de novo paternally derived dicentric X;15 translocation. Her karyotype is therefore 45,X/45,X,dic(X;15)(Xpter-->Xq26.1::15p11-->15 qter) based on G-banding. The presence of 2 centromeres on the derivative X was confirmed by fluorescence in situ hybridization (FISH) and a deletion of Xq26.1-->qter was confirmed by polymerase chain reaction (PCR) using DXS52 and DXYS154. Replication banding studies indicate that the derivative X is late replicating. Based on these studies, it is unclear whether inactivation has spread to proximal 15q. The patient has a unique phenotype distinct from Ullrich-Turner or Prader-Willi syndromes, but includes ataxia and language delay which are commonly seen in Angelman syndrome. These findings are contrary to those anticipated since deficiency of paternal genes at 15q12 typically leads to Prader-Willi syndrome. Molecular analysis of PCR-based polymorphisms of chromosome 15 and X indicates that uniparental disomy is not present for the X chromosome or chromosome 15 in either cell line. It is hypothesized that her phenotype results from the interaction of the 2 abnormal genotypes. Each abnormality may be diluted by the mosaicism and, in the derivative X line, by the possible variation among cells of inactivation spreading to chromosome 15.

Abnormalities, Multiple↗
PubMed1995

De novo tandem duplication of chromosome segment 22q11-q12: clinical, cytogenetic, and molecular characterization.

We report on a case of duplication of the segment 22q11-q12 due to a de novo duplication. Molecular cytogenetics studies demonstrated this to be a tandem duplication, flanked proximally by the marker D22Z4, a centromeric alpha satellite DNA repeat, and distally by D22S260, an anonymous DNA marker proximal to the Ewing sarcoma breakpoint. The segment includes the regions responsible for the "cat-eye," Di George, and velo-cardio-facial syndromes and extends distal to the breakpoint cluster region (BCR). The clinical picture is dominated by the cardiac defects and includes findings reminiscent of "cat-eye" syndrome. These findings reinforce the hypothesis that the proximal 22q region contains dosage-sensitive genes involved in development.

Chromosome Aberrations↗
PubMed1995

Submicroscopic deletions at 22q11.2: variability of the clinical picture and delineation of a commonly deleted region.

DiGeorge anomaly (DGA) and velo-cardiofacial syndrome (VCFS) are frequently associated with monosomy of chromosome region 22q11. Most patients have a submicroscopic deletion, recently estimated to be at least 1-2 Mb. It is not clear whether individuals who present with only some of the features of these conditions have the deletion, and if so, whether the size of the deletion varies from those with more classic phenotypes. We have used fluorescence in situ hybridization (FISH) to assess the deletion status of 85 individuals referred to us for molecular analysis, with a wide range of DGA-like or VCFS-like clinical features. The test probe used was the cosmid sc11.1, which detects two loci about 2 Mb apart in 22q11.2. Twenty-four patients carried the deletion. Of the deleted patients, most had classic DGA or VCFS phenotypes, but 6 deleted patients had mild phenotypes, including 2 with minor facial anomalies and velopharyngeal incompetence as the only presenting signs. Despite the great phenotypic variability among the deleted patients, none had a deletion smaller than the 2-Mb region defined by sc11.1. Smaller deletions were not detected in patients with particularly suggestive phenotypes who were not deleted for sc11.1, even when tested with two other probes from the DGA/VCFS region.

Abnormalities, Multiple↗
PubMed1995

Dysmorphic features in patients with complex glycerol kinase deficiency.

Complex glycerol kinase deficiency is a contiguous gene syndrome consisting of a deletion of the glycerol kinase locus, together with the genes for adrenal hypoplasia congenita or Duchenne muscular dystrophy or both. We describe an infant with complex glycerol kinase deficiency and mildly dysmorphic features similar to those seen in other patients, including an "hourglass" appearance of the middle of the face; hypertelorism; rounded palpebral fissures; esotropia; wide, flattened earlobes; and a downturned mouth. The combination of medical history and characteristic facies should prompt the request for specific laboratory tests diagnostic for this potentially treatable condition.

Adrenal Insufficiency↗
PubMed1995

The gene for a human microfibril-associated glycoprotein is commonly deleted in Smith-Magenis syndrome patients.

Smith-Magenis syndrome (SMS) is a clinically recognizable multiple congenital anomaly/mental retardation syndrome associated with deletion of chromosome 17p11.2. Here we report the identification of a novel gene encoding a human microfibril-associated glycoprotein (MFAP4), which has been mapped to the SMS region. A full-length cDNA corresponding to this gene has been sequenced, and reveals a coding region of 255 amino acids. MFAP4 has a fibrinogen-like domain and shares a high level of sequence homology to a fragment of a bovine 36 kDa microfibril-associated glycoprotein. The N-terminus of the protein bears an Arg-Gly-Asp sequence that serves as the ligand motif for cell surface receptor integrin. These structural features of MFAP4 suggest that it is an extracellular matrix protein involved in cell adhesion or intercellular interactions. Deletion analysis has been conducted on 31 SMS patients by polymerase chain reaction and Southern analysis of somatic cell hybrids retaining the del(17)(p11.2) chromosome or by fluorescence in situ hybridization. The MFAP4 locus is deleted in 30 of 31 SMS patients. Thus, the function of this gene must be considered in the pathogenesis of SMS. Given our previous hypothesis that SMS is a contiguous gene syndrome, complete and exhaustive definition of the critical deletion interval and a thorough phenotype-genotype correlation is required to demonstrate the role and importance of the MFAP4 gene in SMS.

Abnormalities, Multiple↗