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Biomedical subjects

R M Winter

Publications and source records attributed to R M Winter.

At least 19 recordsLinked to original sources
PubMed1992

The mapping of a gene for craniosynostosis: evidence for linkage of the Saethre-Chotzen syndrome to distal chromosome 7p.

Craniosynostosis or premature closure of the cranial sutures is a common abnormality occurring in about 1 in 2500 children. There is evidence of mendelian inheritance in some 20% of cases. Published reports of patients with structural alterations of the short arm of chromosome 7 have suggested that two or more genes for craniosynostosis may be situated in this region. The Saethre-Chotzen syndrome (acrocephalosyndactyly type III) is one of the most common autosomal dominant craniosynostosis syndromes. Results of molecular genetic linkage studies provide evidence for localisation of the gene responsible to distal chromosome 7p.

Acrocephalosyndactylia↗
PubMed1992

Confirmation of an association between RFLPs at the transforming growth factor-alpha locus and non-syndromic cleft lip and palate.

Three RFLPs at the TGFA locus were studied in 60 unrelated British Caucasian subjects with non-syndromic cleft lip/palate and 60 controls. A highly significant association between the TaqI RFLP and the occurrence of clefting was found (chi 2 = 15.04, p = less than 0.001). No significant association was found with the two other RFLPs studied (BamHI and RsaI). Haplotypes derived from the three RFLPs at the TGFA locus also showed an over-representation of the C2A2B2 haplotype in cases compared to controls. Analyses of genotypes according to type of cleft and the presence or absence of a family history of clefting were also carried out. These results provide further support for the role of TGFA as a gene of major effect in the development of orofacial clefts in humans.

Alleles↗
PubMed1992

No evidence of linkage between the transforming growth factor-alpha gene in families with apparently autosomal dominant inheritance of cleft lip and palate.

Eight families have been identified with cleft lip, with or without cleft palate (CL/P), inherited in an apparently autosomal dominant manner. Transforming growth factor-alpha (TGFA) has been tested as a candidate gene for clefting in these families. Negative lod scores were generated in an autosomal dominant model with 80% penetrance (Z = -3.152 at theta = 0.05 and Z = -2.49 at theta = 0.05 with only affected subjects scored). After testing with a reduced penetrance of 28%, less negative lod scores were generated (Z = -0.157 at theta = 0.00), but there was still no evidence of linkage. An autosomal recessive model with a penetrance of 35% was also tested. Regardless of the model used there was little evidence of linkage between TGFA and the CL/P phenotype, which is in contrast to the previously published findings of an association between TGFA and CL/P in unrelated subjects.

Cleft Lip↗
PubMed1992

The acrocallosal syndrome and Greig syndrome are not allelic disorders.

Acrocallosal syndrome is an autosomal recessive form of polysyndactyly associated with mental retardation and agenesis of the corpus callosum. There have been suggestions that it is allelic to the Greig cephalopolysyndactyly syndrome. Linkage analysis, using flanking markers, shows this suggestion is unlikely to be correct.

Abnormalities, Multiple↗
PubMed1992

Pelizaeus-Merzbacher disease: detection of mutations Thr181----Pro and Leu223----Pro in the proteolipid protein gene, and prenatal diagnosis.

A family with an apparent history of X-linked Pelizaeus-Merzbacher disease presented for genetic counseling, requesting carrier detection and prenatal diagnosis. RFLP analysis using the proteolipid protein (PLP) gene probe was uninformative in this family. A prenatal diagnosis on a chorionic villus sample (CVS) was carried out using single-strand conformation polymorphism (SSCP) analysis of a variant in exon 4 of the PLP gene. The fetus was predicted to be unaffected. Sequencing of the exon from the CVS, the predicted-carrier mother, and the obligate-carrier grandmother revealed an A-to-C change at nucleotide 541 in the two women but not in the fetus. As this change results in a Thr-to-Pro change at amino acid 181 in a region of the gene predicted to be part of a transmembrane segment, it was concluded that this was the mutation causing the disease in this family. In addition, in a second family, an exon 5 variant band pattern on SSCP analysis was shown by sequencing to be due to a T-to-C change at nucleotide 668. This results in a Leu-to-Pro change in a carrier mother and in her two affected sons. These results provide further examples of mutations in PLP that cause Pelizaeus-Merzbacher disease and illustrate the value of SSCP in genetic analysis.

Amino Acid Sequence↗
PubMed1991

Short stature/short limb skeletal dysplasia with severe combined immunodeficiency and bowing of the femora: report of two patients and review.

We report two patients with severe combined immunodeficiency and short stature/short limb skeletal dysplasia. Case 1 presented at birth with rhizomelic shortening of the extremities and bowing of the femora. She developed clinical signs of severe combined immunodeficiency at 13 months and died at 21 months. Case 2 had severe prenatal shortening and bowing of the extremities and a small, malformed chest. Symptoms of severe combined immunodeficiency and severe failure to thrive developed soon after birth and she died at 5 months. The diagnosis of severe combined immunodeficiency in our patients was based on their clinical course and necropsy findings, supported in case 1 by the results of immune function tests. The results of investigation of immune function (immunoglobulins, lymphocyte subpopulations, lymphocyte function) are very variable in this syndrome as in other variants of severe combined immunodeficiency. Bone histopathology in both patients showed grossly irregular costochondral junctions, but normal transition of proliferating to hypertrophic chondrocytes. These cases belong to early lethal type 1 short limb skeletal dysplasia with severe combined immunodeficiency. Review of previously published cases with severe combined immunodeficiency and well documented skeletal findings show eight patients with prenatal onset of bowing and shortening of the extremities and metaphyseal abnormalities. These include two sib pairs concordant for the skeletal changes. In these cases, adenosine deaminase levels were not reported. An additional four published cases with associated adenosine deaminase deficiency had only mild metaphyseal abnormalities, but subsequently showed no linear growth.(ABSTRACT TRUNCATED AT 250 WORDS)

Adenosine Deaminase↗
PubMed1991

Oculofacialbulbar palsy in mother and son: review of 26 reports of familial transmission within the 'Möbius spectrum of defects'.

We report a mother and son with 5th, 6th, 7th, and bulbar cranial nerve paralysis, who had two similarly affected relatives. None of them had primary skeletal defects. Twenty-six previous reports of familial cases within the heterogeneous 'Möbius spectrum of defects' were reviewed. When cranial nerve palsies were associated with a primary skeletal defect, familial transmission was not found. No recurrence was noted in 31 cases with cranial nerve palsies associated with oral abnormalities and limb defects. The term Möbius syndrome should be restricted to cases with congenital 6th and 7th nerve paralysis with skeletal defects, who have a low recurrence risk (2%). The features in an index case which may indicate a higher risk of recurrence are the absence of skeletal defects, isolated facial palsy, deafness, ophthalmoplegia, and digital contractures. A recurrence risk of 25 to 30% in these cases appears reasonable.

Adult↗
PubMed1991

Autosomal dominant inheritance of abnormalities of the hands and feet with short palpebral fissures, variable microcephaly with learning disability, and oesophageal/duodenal atresia.

We report two families with an autosomal dominant syndrome of abnormalities of the hands and feet, short palpebral fissures, and variable microcephaly with learning disability. Between a third and a quarter of cases are born with oesophageal atresia, duodenal atresia, or both. Individual patients have hypoplastic thumbs or congenital heart disease. The phenotype of the syndrome reported here is similar to that observed in 13q22-qter deletion patients. However, chromosome analysis has not detected any structural abnormality in our patients.

Duodenal Obstruction↗
PubMed1990

Ellis-van creveld syndrome, Jeune syndrome, and renal-hepatic-pancreatic dysplasia: separate entities or disease spectrum?

We describe two children with multiple abnormalities, neither of whom fits neatly into a classical diagnostic category, but who show overlapping features of Ellis-van Creveld syndrome, Jeune syndrome, and renal-hepatic-pancreatic dysplasia. It seems possible that these three entities form part of a disease spectrum rather than being distinct conditions.

Ellis-Van Creveld Syndrome↗
PubMed1990

The Baller-Gerold syndrome: phenotypic and cytogenetic overlap with Roberts syndrome.

A case is reported where the major clinical features of craniostenosis and radial aplasia led to an initial diagnosis of Baller-Gerold syndrome. Mild fibular hypoplasia on skeletal survey led to review of the diagnosis and the similarity of the facial phenotype to that of Roberts syndrome was noted. Chromosome analysis showed the premature centromere separation characteristic of this condition. This case raises the question as to whether the Baller-Gerold syndrome can be considered as a distinct entity. It is suggested that cases diagnosed as having Baller-Gerold syndrome should have cytogenetic analysis and that known Roberts syndrome survivors are reviewed for signs of craniostenosis.

Adult↗
PubMed1989

Two brothers with facial anomalies, microcephaly, hypoplastic genitalia, and a failure of psychomotor development.

We report on 2 brothers from a consanguineous Moslem family with prenatal onset of growth deficiency, microcephaly, hypoplastic genitalia, and convulsions from birth. Phenotypic anomalies consisted of a prominent glabella, arched eyebrows, a low upswept frontal hairline, a small pinched nose, large posteriorly rotated ears with overfolded upper helices, partial camptodactyly, and widespaced nipples. Psychomotor development was absent, and there was marked failure to thrive. Death occurred at ages 21 days and 7 months, respectively. Postmortem examination on one child showed dilated cerebral ventricles and hydronephrosis. Microcephaly was detectable by fetal ultrasound in one brother at 17 weeks of gestation.

Abnormalities, Multiple↗
PubMed1989

MASA syndrome: further clinical delineation and chromosomal localisation.

MASA syndrome (mental retardation, aphasia, shuffling gait and adducted thumbs) is an X-linked disorder first described in 1974. Since that time, two further pedigrees have been reported with similar features. The main clinical features are summarised by the acronym. Kenwrick et al. reported a separate family with X-linked recessive spastic paraplegia and mental retardation and demonstrated close linkage to DXS15 and DXS52 (DX13 and St14) at Xq28. Four affected individuals in this family were said to have absence of the extensor pollicis longus. Here we report a family where two adult brothers and their nephew have the phenotype of MASA syndrome. We demonstrate by clinical and gene mapping studies that MASA syndrome is most likely the same condition as that described by Kenwrick et al., and we review its clinical course and presentation.

Abnormalities, Multiple↗