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J M Cobben

Publications and source records attributed to J M Cobben.

At least 37 records · Page 2Linked to original sources
PubMed1996

The EEC syndrome: a literature study.

Analysis of 230 published cases of the EEC syndrome revealed that, besides the cardinal symptoms (ectrodactyly, ectodermal dysplasia and clefting), lacrimal tract abnormalities and urogenital abnormalities are part of this syndrome. Mental retardation and various abnormalities and dysmorphisms of the ears and face, reported in EEC syndrome, do not really seem to be part of it. Conductive hearing loss is associated with clefting. A score for the severity of symptoms in the EEC syndrome is described, and using this score it appears that isolated cases are generally more severely affected than familial cases. We did not find signs of genomic imprinting or anticipation in published EEC families. We did find, however, that interfamilial variability is significantly larger than intrafamilial variability, pointing to genetic (allelic?) heterogeneity. The penetrance of the EEC-mutation is estimated to be between 93% and 98%.

Abnormalities, Multiple↗
PubMed1996

Apparent gene conversions involving the SMN gene in the region of the spinal muscular atrophy locus on chromosome 5.

The survival motor neuron (SMN) gene has been described as a determining gene for spinal muscular atrophy (SMA). SMN has a closely flanking, nearly identical copy (cBCD541). Gene and copy gene can be discriminated by sequence differences in exons 7 and 8. The large majority of SMA patients show homozygous deletions of at least exons 7 and 8 of the SMN gene. A minority of patients show absence of SMN exon 7 but retention of exon 8. This is explained by results of our present analysis of 13 such patients providing evidence for apparent gene-conversion events between SMN and the centromeric copy gene. Instead of applying a separate analysis for absence or presence of SMN exons 7 and 8, we used a contiguous PCR from intron 6 to exon 8. In every case we found a chimeric gene with a fusion of exon 7 of the copy gene and exon 8 of SMN and absence of a normal SMN gene. Similar events, including the fusion counterpart, were observed in a group of controls, although in the presence of a normal SMN gene. Chimeric genes as the result of fusions of parts of SMN and cBCD541 apparently are far from rare and may partly explain the frequently observed SMN deletions in SMA patients.

Chromosomes, Human, Pair 5↗
PubMed1996

Prenatal prediction of spinal muscular atrophy. Experience with linkage studies and consequences of present SMN deletion analysis.

With the localisation of the gene for the autosomal recessive forms of proximal spinal muscular atrophies (SMA) to the chromosomal region 5q13 and the later detection of homozygous deletions of the SMN gene located in this region, prenatal prediction of SMA has become feasible and is widely applied now. In our experience with 77 prenatal predictions of SMA, follow-up of the 39 liveborn children from these pregnancies never led to a false-negative result. Application of SMN deletion analysis has consequences for prenatal prediction of SMA. When the index patient has a homozygously deleted exon 7 of the SMN gene, prenatal prediction and interpretation of results are straightforward. In families in which no DNA from the index patient is available, prenatal detection of a homozygous SMN deletion may be considered almost proof of SMA in the fetus. Absence of a deletion, however, will not guarantee an unaffected child. A real problem exists if the index patient does not show a homozygous deletion of SMN exon 7. In such cases with non-homozygous SMN deletions, one cannot be certain of 5q linkage and autosomal recessive inheritance until other SMN mutations are detected. This is an argument to abstain from prenatal diagnosis by linkage analysis in these families.

Chromosomes, Human, Pair 5↗
PubMed1995

Trisomy 1q42 --> qter in a sister and brother: further delineation of the "trisomy 1q42 --> qter syndrome".

We report on a 22-year-old woman and her 21-year-old brother with mild mental retardation, long face, prominent forehead, retrognathia, and (relative) macrocephaly. At birth they were small for date, their length is now below the 10th centile. Chromosome analysis demonstrated a nearly pure trisomy 1q42 --> qter in both patients due to unbalanced segregation of a paternal reciprocal balanced translocation 46,XY,t(1;15) (q42;p11). This is the second report of a nearly pure trisomy 1q42 --> qter. When comparing the manifestations of our patients with those of other reported cases we conclude that the most characteristic clinical manifestations of this syndrome are macrocephaly, prominent forehead, micro/retrognathia, large fontanelle, intrauterine growth retardation, postnatal growth retardation, and mental retardation.

Adult↗
PubMed1995

A sublocus of the multicopy microsatellite marker CMS1 maps proximal to spinal muscular atrophy (SMA) as shown by recombinant analysis.

The critical region containing the spinal muscular atrophy (SMA) gene is flanked by the 5q11-q13 markers, D5S435 and D5S557, as determined by linkage analysis. Here we present the results of an analysis of a Dutch SMA family with the multicopy microsatellite marker CMS1. A crossover is revealed in the critical SMA region. We conclude that at least one of the CMS1 subloci maps proximal to the SMA gene. This reduces the minimal SMA region from approximately 1.4 Mb to 600-700 kb.

Chromosome Mapping↗
PubMed1995

Variable expression of the popliteal pterygium syndrome in two 3-generation families.

Three successive generations in two families affected with the popliteal pterygium syndrome are reported. While expression of the syndrome was relatively mild in the first and second generation, the patients in the third generation showed the full-blown syndrome. Differential diagnosis between mildly affected patients with the popliteal pterygium syndrome and those with Van der Woude syndrome is difficult and may even be impossible. The present observations further support the hypothesis that both syndromes may in fact represent variants of the same condition.

Abnormalities, Multiple↗
PubMed1995

Bilateral split hand/foot malformation and inv(7)(p22q21.3).

A boy with typical tetramelic split hands and feet is described. In addition, there was a large arteriovenous malformation of the right arm. Chromosome studies showed a pericentric inversion of chromosome 7: 46,XY,inv(7)(p22q21.3). Inspection of the extremities and chromosome studies in the parents were normal. This case confirms the suggested localisation of a locus, important for early limb differentiation, on the long arm of chromosome 7, most probably in the chromosomal region 7q21.2-7q21.3. Previously reported cases are reviewed briefly.

Child, Preschool↗
PubMed1995

Deletions of the survival motor neuron gene in unaffected siblings of patients with spinal muscular atrophy.

DNA studies in 103 spinal muscular atrophy (SMA) patients from The Netherlands revealed homozygosity for a survival motor neuron (SMN) deletion in 96 (93%) of 103. Neuronal apoptosis inhibitory protein deletions were found in 38 (37%) of 103 and occurred most frequently in SMA type I. SMN deletions have not yet been described to occur in healthy subjects. In this study, however, four unaffected sibs from two SMA families showed homozygosity for SMN deletions. Homozygosity for an SMN deletion in unaffected persons seems to be very rare. Therefore, demonstration of a homozygous SMN deletion in a clinically presumed SMA patient should be considered as a confirmation of the diagnosis, whether or not SMN is in fact the causal gene for SMA.

DNA↗
PubMed1994

Identification of key recombinants in multiplex SMA families.

Recent reports have provided evidence that a major gene for autosomal recessive proximal spinal muscular atrophy (SMA) resides in a small genetic interval in bands q12-q13 of chromosome 5, a 4-cM region proximally flanked by D5S125 (EF(TG/AG)n) and distally by MAP1B/D5S112 or a 0.7-cM interval (range 0.1-2.1 cM) flanked by D5S435 proximally and MAP1B/D5S112 distally. We present the identification of key recombinants between SMA and the closest flanking DNA-markers in an analysis of Dutch and Italian SMA families. These crossovers may serve as reference points for new markers in this region and may thus be instrumental in a further refined mapping of the SMA gene. Two markers, D5S351 (I105) and D5S357 (Mfd151), could be mapped distally to SMA in the interval SMA-D5S112.

Chromosome Mapping↗
PubMed1994

The popliteal pterygium syndrome: an analysis of two families.

The popliteal pterygium syndrome is characterized by multiple anomalies of the face, genito-urinary system and extremities with autosomal dominant inheritance with variable expression. Also sporadic cases probably based upon spontaneous mutation can be recognized. The plastic, orthopaedic, and maxillofacial surgeon should be aware of the variable nature of the syndrome and should consult a medical geneticist. A coordinated team approach appears to be most adequate for diagnosis, counselling and treatment.

Abnormalities, Multiple↗
PubMed1994

Apparent SMA I unlinked to 5q.

A proband with a clinical picture indistinguishable from SMA type I is described. The parents are second cousins. On DNA analysis it appeared that the proband and his healthy 2 year old sib had inherited the same haplotypes for DNA markers flanking the SMA locus on 5q. This supports non-linkage of SMA to chromosome 5q in this family. The consanguinity of the parents raises the possibility of a second locus for autosomal recessive SMA type I outside the 5q12-13 region. This may have implications for genetic counselling after prenatal diagnosis in consanguineous families. Furthermore, this case illustrates the importance of the inclusion of all healthy sibs in prenatal DNA studies for SMA type I.

Chromosomes, Human, Pair 5↗
PubMed1994

Genetic counseling in limb reduction defects.

During several years experience in a multidisciplinary out-patient clinic for children with congenital hand malformations a systematic approach was devised to arrive at an accurate diagnosis and recurrence risk in patients with congenital limb reduction defects. Classification and diagnostic work-up was done according to a protocol, derived from data in the literature and from our own experience. This protocol is described for the different types of congenital upper limb reduction defects.

Ectromelia↗
PubMed1994

Fluorescence in situ hybridisation on formalin fixed fetal tissue in the diagnosis of chromosomal syndromes.

Two cases of stillborn children with multiple congenital anomalies are presented. No routine karyotyping was performed. After dysmorphologic evaluation a tentative diagnosis of trisomy 18 and triploidy, respectively, could be made. Fluorescence in situ hybridisation with several chromosome specific probes on formalin fixed paraffin embedded tissue confirmed the suspected diagnosis in both cases. In view of the important consequences for the parents (relatively low recurrence risk, availability of prenatal diagnosis in subsequent pregnancies) fluorescence in situ hybridisation for the common chromosomal aneuploidies should be performed in selected cases of stillborn fetuses with multiple congenital malformations.

Abnormalities, Multiple↗
PubMed1993

Linkage and apparent heterogeneity in proximal spinal muscular atrophies.

Linkage studies with 9 highly informative DNA markers on the long arm of chromosome 5 were performed in 12 multiplex families (29 patients) with spinal muscular atrophy (SMA) from The Netherlands. The results of the linkage analysis were compatible with localization of a major SMA gene in the chromosomal region 5q12-13. By minimum recombinant analysis the most likely position of the SMA locus was between loci D5S6/D5S125 and D5S112/MAP1B, which is in agreement with several linkage studies from other countries. In four families, however, more than one crossover between SMA and a flanking DNA marker appeared, and in one family the observed hybridization phenotype for the markers closely flanking the SMA locus was identical for an unaffected individual and for his two affected sibs with SMA type III. For this latter family, among several explanations the most likely are either the presence of a double crossover or linkage heterogeneity.

Chromosome Mapping↗