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E Passarge

Publications and source records attributed to E Passarge.

At least 19 recordsLinked to original sources
PubMed2001

Girl with phenotypic abnormalities and a de novo, apparently balanced translocation 46,XX,t(5;10)(q35.2q11.2).

We describe a three-year-old girl with a triangular face, epicanthus, midfacial hypoplasia, apparently low-set ears, a small mouth with thin vermilion border, and a small chin, hypermobile joints, developmental delay with insecure gait, dystonic movement disorder, speech defect, and a history of unexplained undernutrition. She has a de novo, apparently balanced translocation t(5;10)(q35.2;q11.2). Using fluorescence in situ hybridization (FISH), we located the breakpoints in the 1.5-Mb area defined by YAC 753f5 (5q35.2) and within the approximately 2-Mb interval between 10cen and YAC 933a3 (10q11.21).

Child, Preschool↗
PubMed2001

[Analysis of a case of balanced chromosome translocation and phenotypic abnormality by fluorescence in situ hybridization].

OBJECTIVE: To delineate the chromosome structural aberration in a case of chromosome translocation by fluorescence in situ hybridization(FISH) technique and precisely identify the breakpoints. METHODS: The whole chromosome point 5(wcp5) and locus- specific probes derived from yeast artificial chromosomes(YACs) mapping the nearby region of breakpoints were used to delineate the translocation t(5;10) found by high resolution G-banding examination in a case with congenital abnormality. RESULTS: A balanced translocation was confirmed and the breakpoints were located in the 1.5 Mb area on chromosome 5 and within the approximately 3 Mb interval on chromosome 10. CONCLUSION: The phenotypic abnormality might result from the disruption of disease-associated gene(s) or microrearrangement(s) on the site of breakpoint(s).

Child, Preschool↗
PubMed2000

A distinctive phenotype associated with an interstitial deletion 6q14 contained within a de novo pericentric inversion 6 (p11.2q15).

This report describes a nearly 25-year-old female with an interstitial deletion of band 14 in the long arm of one chromosome 6 (6q14). The deletion is contained within a de novo pericentric inversion with breakpoints in 6p11.2 and 6q15 (Karyotype 46,XX, del(6)(q13q15),inv(6)(p11.2q15). The distal breakpoint of the deletion and the pericentric inversion at 6q15 are the same, but the proximal breakpoints differ. Since cells with other chromosomal findings were not detected in cultured lymphocytes and fibroblasts, chromosome mosaicism seems unlikely. Thus, it is assumed that the inversion and the deletion originated from the same event. The development of a distinctive phenotype in the patient was observed over a period of 22 years. It includes characteristic dysmorphic facial features such as ocular hypertelorism, flat nasal bridge, prominent zygomatic bones, and a depressed glabella. A striking, non-progressive deficit of motor control is manifest in an inability to use her hands properly and a broad-based slow-motion-like gait. Although severely deficient in abstract mental abilities and speech development, she is well adapted to family life and to a school for retarded individuals. Normal height and head circumference, and reduced sensitivity to pain are noteworthy. Presumably the deletion caused the phenotype and the distinct behavioral pattern. This patient probably represents a novel chromosomal phenotype that results from aggregate haploinsufficiency of gene loci in the deleted region.

Abnormalities, Multiple↗
PubMed1998

Analysis of a familial three way translocation involving chromosomes 3q, 6q, and 15q by high resolution banding and fluorescent in situ hybridisation (FISH) shows two different unbalanced karyotypes in sibs.

We report on a familial three way translocation involving chromosomes 3, 6, and 15 identified by prometaphase banding and fluorescence in situ hybridisation (FISH). Two mentally retarded sibs with different phenotypic abnormalities, their phenotypically normal sister and mother, and two fetuses of the phenotypically normal sister were analysed. The terminal regions of chromosomes 3q, 6q, and 15q were involved in a reciprocal translocation, in addition to a paracentric inversion of the derivative chromosome 15. Conventional cytogenetic studies with high resolution GTG banding did not resolve this rearrangement. FISH using whole chromosome paints (WCPs) identified the chromosomal regions involved, except the aberrant region of 3q, which was undetectable with these probes. Investigation of this region with the subtelomeric FISH probe D3S1445/D3S1446 showed a balanced karyotype, 46,XX,t(3;15;6) (q29;q26.1;q26), inv der(15) (q15.1q26.1) in two adult females and one fetus. It was unbalanced in two sibs, showing two different types of unbalanced translocation resulting in partial trisomy 3q in combination with partial monosomy 6q in one patient and partial trisomy 15q with partial monosomy 6q in the other patient and one fetus. These represent apparently new chromosomal phenotypes.

Adult↗
PubMed1997

Three brothers with mental and physical retardation, hydrocephalus, microcephaly, internal malformations, speech disorder, and facial anomalies: Mutchinick syndrome.

We describe three brothers from a non-consanguineous family with microcephaly, mental and physical retardation, speech disorder, facial anomalies, and internal hydrocephalus in two of the three affected brothers. The youngest brother died at the age of 5 months. He had situs abdominalis inversus, ASD II, and had been operated for internal hydrocephalus and atresia of the biliary duct. A search in the Oxford Medical Database Dysmorphology Program suggested phenotypic similarities with two sisters described in 1972 by Osvaldo Mutchinick in Argentina. Although differences in their phenotypes exist, it is possible that the two sets of sibs represent the same, rare syndrome. This interpretation is supported by the origin of both families from the same geographic region.

Abnormalities, Multiple↗
PubMed1997

[Molecular genetics and diagnosis of retinoblastoma. Significance for ophthalmologic practice].

Retinoblastoma (RB) is initiated by loss of function of both copies of the retinoblastoma susceptibility gene (RB 1). Hereditary predisposition to RB is caused by germline mutations in the RB 1 gene. Tumor formation is initiated by the somatic loss of the second allele. Most patients with hereditary RB develop multiple tumors that usually affect both eyes. In nonhereditary disease, however, both RB 1 mutations are somatic events that cause the formation of a single tumor focus. Knowledge of the germline mutation is often essential for accurate risk prediction. Applying strategies for efficient mutation detection, germline mutations can be identified in most individuals with hereditary RB. The vast majority of mutant alleles cause premature termination of translation owing to frameshift or nonsense mutations. In patients carrying these mutant alleles, penetrance is almost complete (> 95%) and numerous tumor foci are observed. However, some 5% of the mutations result in comparatively mild alterations at the protein level. Patients with mutations of this kind often show a lower mean number of tumor foci (reduced expressivity) or no tumor at all (incomplete penetrance). Reduced expressivity and incomplete penetrance are also observed in patients with large cytogenetic deletions. By mutation analysis in DNA from fresh frozen tumor samples and peripheral blood, we have detected RB 1 germline mutations in some 20% of patients with unilateral RB. These results emphasize the importance of molecular analysis in patients with isolated unilateral RB.

Chromosomes, Human, Pair 13↗
PubMed1997

Distinct spectrum of CFTR gene mutations in congenital absence of vas deferens.

Congenital absence of the vas deferens (CAVD) is a frequent cause for obstructive azoospermia and accounts for 1%-2% of male infertility. A high incidence of mutations of the cystic fibrosis transmembrane conductance regulator (CFTR) gene has recently been reported in males with CAVD. We have investigated a cohort of 106 German patients with congenital bilateral or unilateral absence of the vas deferens for mutations in the coding region, flanking intron regions and promotor sequences of the CFTR gene. Of the CAVD patients, 75% carried CFTR mutations or disease-associated CFTR variants, such as the "5T" allele, on both chromosomes. The distribution of mutation genotypes clearly differed from that observed in cystic fibrosis. None of the CAVD patients was homozygous for delta F508 and none was compound heterozygous for delta F508 and a nonsense or frameshift mutation. Instead, homozygosity was found for a few mild missense or splicing mutations, and the majority of CAVD mutations were missense substitutions. Twenty-one German CAVD patients were compound heterozygous for delta F508 and R117H, which was the most frequent CAVD genotype in our study group. Haplotype analysis indicated a common origin for R117H in our population, whereas another frequent CAVD mutation, viz. the "5T allele" was a recurrent mutation on different intragenic haplotypes and multiple ethnic backgrounds. We identified a total of 46 different mutations and variants, of which 15 mutations have not previously been reported. Thirteen novel missense mutations and one unique amino-acid insertion may be confined to the CAVD phenotype. A few splice or missense variants, such as F508C or 1716 G-->A, are proposed here as possible candidate CAVD mutations with an apparently reduced penetrance. Clinical examination of patients with CFTR mutations on both chromosomes revealed elevated sweat chloride concentrations and discrete symptoms of respiratory disease in a subset of patients. Thus, our collaborative study shows that CAVD without renal malformation is a primary genital form of cystic fibrosis in the vast majority of German patients and links the particular expression of clinical symptoms in CAVD with a distinct subset of CFTR mutation genotypes.

Adult↗
PubMed1997

Constitutional RB1-gene mutations in patients with isolated unilateral retinoblastoma.

In most patients with isolated unilateral retinoblastoma, tumor development is initiated by somatic inactivation of both alleles of the RB1 gene. However, some of these patients can transmit retinoblastoma predisposition to their offspring. To determine the frequency and nature of constitutional RB1-gene mutations in patients with isolated unilateral retinoblastoma, we analyzed DNA from peripheral blood and from tumor tissue. The analysis of tumors from 54 (71%) of 76 informative patients showed loss of constitutional heterozygosity (LOH) at intragenic loci. Three of 13 uninformative patients had constitutional deletions. For 39 randomly selected tumors, SSCP, hetero-duplex analysis, sequencing, and Southern blot analysis were used to identify mutations. Mutations were detected in 21 (91%) of 23 tumors with LOH. In 6 (38%) of 16 tumors without LOH, one mutation was detected, and in 9 (56%) of the tumors without LOH, both mutations were found. Thus, a total of 45 mutations were identified in tumors of 36 patients. Thirty-nine of the mutations-including 34 small mutations, 2 large structural alterations, and hypermethylation in 3 tumors-were not detected in the corresponding peripheral blood DNA. In 6 (17%) of the 36 patients, a mutation was detected in constitutional DNA, and 1 of these mutations is known to be associated with reduced expressivity. The presence of a constitutional mutation was not associated with an early age at treatment. In 1 patient, somatic mosaicism was demonstrated by molecular analysis of DNA and RNA from peripheral blood. In 2 patients without a detectable mutation in peripheral blood, mosaicism was suggested because 1 of the patients showed multifocal tumors and the other later developed bilateral retinoblastoma. In conclusion, our results emphasize that the manifestation and transmissibility of retinoblastoma depend on the nature of the first mutation, its time in development, and the number and types of cells that are affected.

Actuarial Analysis↗
PubMed1996

Microcephaly, seizures, genital hypoplasia, and abnormalities of the hands and feet in a 4-year-old boy with possible Wiedemann syndrome.

We report on a 4-year-old boy with short stature, microcephaly, BNS (Blitz-Nick-Salaam) seizures, and global developmental delay. In addition, small and fleshy hands and feet as well as hypoplastic scrotum and testes were observed. The clinical features of the patient are compared with the patients previously described by Wiedemann et al. and Nevin et al. They reported three patients with a syndrome characterized by short stature, microcephaly, global developmental delay, abnormalities of hands and feet, seizures, large anterior fontanelle, scrotal hypoplasia, micropenis, cryptorchism, urinary tract abnormalities, and inguinal hernia (Wiedemann syndrome).

Abnormalities, Multiple↗
PubMed1996

The spectrum of RB1 germ-line mutations in hereditary retinoblastoma.

We have searched for germ-line RB1 mutations in 119 patients with hereditary retinoblastoma. Previous investigations by Southern blot hybridization and PCR fragment-length analysis had revealed mutations in 48 patients. Here we report on the analysis of the remaining 71 patients. By applying heteroduplex analysis, nonisotopic SSCP, and direct sequencing, we detected germ-line mutations resulting in premature termination codons or disruption of splice signals in 51 (72%) of the 71 patients. Four patients also showed rare sequence variants. No region of the RB1 gene was preferentially involved in single base substitutions. Recurrent transitions were observed at most of the 14 codons within the RB1. No mutation was observed in exons 25-27, although this region contains two CGA codons. This suggests that mutations within the 3'-terminal region of the RB1 gene may not be oncogenic. When these data were combined with the results of our previous investigations, mutations were identified in a total of 99 (83%) of 119 patients. The spectrum comprises 15% large deletions, 26% small length alterations, and 42 % base substitutions. No correlation between the location of frameshift or nonsense mutations and phenotypic features, including age at diagnosis, the number of tumor foci, and manifestation of nonocular tumors was observed.

Adolescent↗
PubMed1995

Genotype-phenotype correlation in a series of 167 deletion and non-deletion patients with Prader-Willi syndrome.

A total of 167 patients with Prader-Willi syndrome (PWS) was studied at the clinical and molecular level. Diagnosis was confirmed by the PW71 methylation test. Quantitative Southern blot hybridizations with a probe for the small nuclear ribonucleoprotein N were performed to distinguish between patients with a deletion (116 patient or 69.5%) and patients without a deletion (51 patients or 30.5%). These two types of patients differed with respect to the presence of hypopigmentation, which was more frequent in patients with a deletion (52%) than in patients without (23%), and to average birth weight of females and males, which was lower in patients with a deletion than in patients without. Newborns with PWS had a lower birth weight and length at term, but normal head circumference in comparison with a control group. This finding aids the identification of the neonatal phenotype. In addition, our data confirm an increased maternal age in the non-deletion group.

Adolescent↗
PubMed1995

DNA methylation based testing of 450 patients suspected of having Prader-Willi syndrome.

Using a test based on parent of origin specific DNA methylation at the D15S63 (PW71) locus, we studied 385 patients (aged 1 to 36 years) for diagnostic confirmation of Prader-Willi syndrome (PWS) and 65 infants (aged 0 to 12 months) with severe hypotonia of unknown cause. Fifty eight of 385 patients were examined personally; 28/58 patients had PWS and lacked the paternal PW71 band and 30/58 patients, who did not have PWS, had a normal methylation pattern. In five of these patients, a differential diagnosis was made (Ohdo-like blepharophimosis syndrome, Alstrøm syndrome, Cohen syndrome, Bardet-Biedl syndrome, and pseudohypoparathyroidism). A total of 327/385 blood samples was sent to us from outside. The test confirmed the diagnosis of PWS in 112/327 patients. Most of the other 215 patients lacked the major diagnostic criteria such as neonatal hypotonia, feeding problems, characteristic facies, and hypogenitalism. On the other hand, 29/65 hypotonic infants tested positive for PWS. We conclude that the PW71 methylation test detects most, if not all, patients with typical PWS and that PWS is often not recognised in infants and wrongly suspected in obese and mentally retarded patients.

Adolescent↗