Biomedical subjects

S Schuffenhauer

Publications and source records attributed to S Schuffenhauer.

45 records · Page 3Linked to original sources

PubMed1994

Tetrasomy 21 pter-->q22.1 and Down syndrome: molecular definition of the region.

Down syndrome is usually caused by complete trisomy 21. Rarely, it is due to partial trisomy of the segment 21q22. We report on a 33-month-old girl with tetrasomy 21 pter-->q22.1 resulting from an extra chromosome idic(21)(q22.1). She has craniofacial traits typical of Down syndrome, including brachycephaly, third fontanel, upward slanting palpebral fissures, round face, and protruding tongue. Speech development is quite delayed whereas motor development is only mildly retarded. The molecular content of the extra isodicentric chromosome was defined by molecular genetic investigations using 13 single copy probes unique to chromosome 21, and SOD1 expression studies. The child was found to have 4 copies of the region defined by D21S16 (21cen) through D21S93 on 21q22.1 and two copies of the remaining region defined by SOD1-->D21S55-->D21S123. In view of the recent assignment of Down syndrome facial characters to the 21q22 region, defined in part by D21S55, it is significant that this child shows a subset of Down syndrome facial manifestations, without duplication of this region. These results suggest that genes contributing to the facial and some of the hand manifestations of Down syndrome also exist in the chromosomal region proximal to D21S55 in band 21q22.1.

Blotting, Southern↗

PubMed1994

[Dyskeratosis congenita in monozygous twins].

Dyskeratosis congenita (DC) is a very rare form of genodermatosis with variable manifestations, which mainly affects male patients. The main clinical symptoms are poikilodermia, nail dystrophy and leucoplakia; there are many other cutaneous and systemic symptoms. To avoid complications and improve the prognosis early diagnosis and regular close surveillance of the patients are important. We report on 13-year-old monozygotic twin brothers who, in addition to the typical symptoms, had increased vulnerability of the skin, scarring of the hands and atrophy of the oral mucosa as well as splenomegaly, pancytopenia with severe aplasia of bone marrow and aseptic necrosis of the hip. The two brothers had nearly synchronous clinical manifestation and progression. This paper reviews the clinical symptoms, pathogenesis, differential diagnosis and genetic aspects of DC.

Adolescent↗

PubMed1994

The mouse pink-eyed dilution gene: association with hypopigmentation in Prader-Willi and Angelman syndromes and with human OCA2.

Mutations at the mouse pink-eyed dilution locus, p, cause hypopigmentation. We have cloned the mouse p gene cDNA and the cDNA of its human counterpart, P. The region of mouse chromosome 7 containing the p locus is syntenic with human chromosome 15q11-q13, a region associated with Prader-Willi syndrome (PWS) and Angelman syndrome (AS), both of which involve profound imprinting effects. PWS patients lack sequences of paternal origin from 15q, whereas AS patients lack a maternal copy of an essential region from 15q. However, the critical regions for these syndromes are much smaller than the chromosomal region commonly deleted that often includes the P gene. Hypopigmentation in PWS and AS patients is correlated with deletions of one copy of the human P gene that is highly homologous with its mouse counterpart. A subset of PWS and AS patients also have OCA2. These patients lack one copy of the P gene in the context of a PWS or AS deletion, with a mutation in the remaining chromosomal homologue of the P gene. Mutations in both homologues of the P gene of OCA2 patients who do not have PWS or AS have also been detected.

Albinism, Oculocutaneous↗

PubMed1993

High resolution mapping of interstitial long arm deletions of chromosome 16: relationship to phenotype.

The breakpoints of seven interstitial deletions of the long arm of chromosome 16 and two ring chromosomes of this chromosome were mapped by in situ hybridisation or by analysis of mouse/human somatic cell hybrids containing the deleted chromosome 16. Use of a high resolution cytogenetic based physical map of chromosome 16 enabled breakpoints to be assigned to an average resolution of at least 1.6 Mb. In general, interstitial deletions involving q12 or q22.1 have broadly similar phenotypes though there are differences in specific abnormalities. Deletions involving regions more distal, from 16q22.1 to 16q24.1, were associated with relatively mild dysmorphism. One region of the long arm, q24.2 to q24.3, was not involved in any deletion, either in this study or in any previous report. Presumably, monosomy for this region is lethal. In contrast, patients with deletions of 16q21 have a normal phenotype. These results are consistent with the proposed distribution of genes, frequent in telomeric Giesma light band regions but infrequent in G positive bands.

Abnormalities, Multiple↗

PubMed1993

Analysis of a terminal Xp22.3 deletion in a patient with six monogenic disorders: implications for the mapping of X linked ocular albinism.

The molecular characterisation of chromosomal aberrations in Xp22.3 has established the map position of several genes with mutations resulting in diverse phenotypes such as short stature (SS), chondrodysplasia punctata (CDPX), mental retardation (MRX), ichthyosis (XLI), and Kallmann syndrome (KAL). We describe the clinical symptoms of a patient with a complex syndrome compatible with all these conditions plus ocular albinism (OA1). He has a terminal Xp deletion of at least 10 Mb of DNA. Both the mother and sister of the patient are carriers of the deletion and show a number of traits seen in Turner's syndrome. The diagnosis of ocular albinism was confirmed in the patient and his mother, who shows iris translucency, patches and streaks of hypopigmentation in the fundus, and macromelanosomes in epidermal melanocytes. By comparative deletion mapping we can define a deletion interval, which locates the OA1 gene proximal to DXS143 and distal to DXS85, with the breakpoints providing valuable starting points for cloning strategies.

Abnormalities, Multiple↗

PubMed1993

Increased parental ages and uniparental disomy 15: a paternal age effect?

Parental ages associated with both maternal and paternal uniparental disomy (UPD) of chromosome 15 are highly elevated in comparison to Zurich population-based controls, with mean maternal and paternal ages of 35.6 and 38.1, respectively for UPD patients (diagnosed in Zurich) and 28.0 and 31.0, in controls. The parental ages are also significantly higher than observed for trisomies of other chromosomes diagnosed in Zurich. The higher age of UPD cases may be due to the fact that two errors, both a gain and a loss of a chromosome 15, are necessary. We suggest that gamete complementation, zygote formation from two gametes one of which is nullisomic and the other disomic for the same chromosome, may be a major mechanism of UPD formation, as well as secondary loss of a chromosome in a trisomic conception, and that there is an association between increased paternal age and nondisjunction.

Adult↗

PubMed1993

[Incontinentia pigmenti in a male patient].

Incontinentia pigmenti (Bloch-Sulzberger syndrome) is a rare genetic disorder usually affecting females. Familial cases show an X-linked dominant inheritance with male lethality. The typical skin manifestations occur in several stages and can be associated with various extracutaneous anomalies. We report on a 10-month-old male patient with incontinentia pigmenti (IP) and a normal male karyotype. Besides the typical cutaneous lesions no other signs have been found so far. IP in male patients can be explained by the presence of Klinefelter syndrome, by the half-chromatid mutation model, or by an early somatic mutation. On the basis of this case report we discuss the clinical findings in and the genetics of IP.

Biopsy↗

PubMed1992

De novo interstitial deletion 16(q12.1q13) of paternal origin in a 10-year-old boy.

A 10-year-old boy with a de novo del(16)(q12.1q13) and many features of the deletion 16q phenotype is described. The deletion occurred in a paternal chromosome as demonstrated by DNA studies with polymorphic (AC)n microsatellite repeat markers. Comparison with published cases suggests that deletion of either of two regions (q13 and q22.1) on the long arm of chromosome 16 is associated with an apparently identical phenotype. No parental imprinting of this region was demonstrated.

Abnormalities, Multiple↗

PubMedDate not supplied

Deletion mapping on chromosome 10p and definition of a critical region for the second DiGeorge syndrome locus (DGS2).

DiGeorge syndrome (DGS) is a developmental field defect, characterised by absent/hypoplastic thymus and parathyroid, and conotruncal heart defects, with haploinsufficiency loci at 22q (DGS1) and 10p (DGS2). We performed fluorescence in situ hybridisations (FISH) and polymerase chain reaction (PCR) analyses in 12 patients with 10p deletions, nine of them with features of DGS, and in a familial translocation 10p;14q associated with midline defects. The critical DGS2 region is defined by two DGS patients, and maps within a 1 cM interval including D10S547 and D10S585. The other seven DGS patients are hemizygous for both loci. The breakpoint of the reciprocal translocation 10p;14q maps at a distance of at least 12 cM distal to the critical DGS2 region. Interstitial and terminal deletions described are in the range of 10-50 cM and enable the tentative mapping of loci for ptosis and hearing loss, features which are not part of the DGS clinical spectrum.

Cell Line, Transformed↗