Search PubMed⌕ Search

Biomedical subjects

R J Gorlin

Publications and source records attributed to R J Gorlin.

At least 37 records · Page 2Linked to original sources
PubMed1998

Mutation spectrum and genotype-phenotype analyses in Cowden disease and Bannayan-Zonana syndrome, two hamartoma syndromes with germline PTEN mutation.

The tumour suppressor gene PTEN , which maps to 10q23.3 and encodes a 403 amino acid dual specificity phosphatase (protein tyrosine phosphatase; PTPase), was shown recently to play a broad role in human malignancy. Somatic PTEN deletions and mutations were observed in sporadic breast, brain, prostate and kidney cancer cell lines and in several primary tumours such as endometrial carcinomas, malignant melanoma and thyroid tumours. In addition, PTEN was identified as the susceptibility gene for two hamartoma syndromes: Cowden disease (CD; MIM 158350) and Bannayan-Zonana (BZS) or Ruvalcaba-Riley-Smith syndrome (MIM 153480). Constitutive DNA from 37 CD families and seven BZS families was screened for germline PTEN mutations. PTEN mutations were identified in 30 of 37 (81%) CD families, including missense and nonsense point mutations, deletions, insertions, a deletion/insertion and splice site mutations. These mutations were scattered over the entire length of PTEN , with the exception of the first, fourth and last exons. A 'hot spot' for PTEN mutation in CD was identified in exon 5 that contains the PTPase core motif, with 13 of 30 (43%) CD mutations identified in this exon. Seven of 30 (23%) were within the core motif, the majority (five of seven) of which were missense mutations, possibly pointing to the functional significance of this region. Germline PTEN mutations were identified in four of seven (57%) BZS families studied. Interestingly, none of these mutations was observed in the PTPase core motif. It is also worthy of note that a single nonsense point mutation, R233X, was observed in the germline DNA from two unrelated CD families and one BZS family. Genotype-phenotype studies were not performed on this small group of BZS families. However, genotype-phenotype analysis inthe group of CD families revealed two possible associations worthy of follow-up in independent analyses. The first was an association noted in the group of CD families with breast disease. A correlation was observed between the presence/absence of a PTEN mutation and the type of breast involvement (unaffected versus benign versus malignant). Specifically and more directly, an association was also observed between the presence of a PTEN mutation and malignant breast disease. Secondly, there appeared to be an interdependent association between mutations upstream and within the PTPase core motif, the core motif containing the majority of missense mutations, and the involvement of all major organ systems (central nervous system, thyroid, breast, skin and gastrointestinal tract). However, these observations would need to be confirmed by studying a larger number of CD families.

Chromosome Mapping↗
PubMed1997

Microcephaly with agenesis of corticospinal tracts and arthrogryposis, hypospadias, single umbilical artery, hypertelorism, and renal and adrenal hypoplasia--previously undescribed syndrome.

We describe a small, term, male infant with corticospinal tract aplasia secondary to motor cortex dysplasia from a neuronal proliferation and/or migrational defect. The infant also had microdolichocephaly, sloping forehead, hypertelorism, flat nose, apparently low-set ears, micrognathia, arthrogryposis without muscle wasting, cortical thumbs, rocker-bottom feet, scoliosis, single umbilical artery, and hypospadias with chordee. Oligohydramnios was present prenatally. Neurologic examination showed a comatose state, seizures, minimal spontaneous movement, minimal response to pain, and absent primitive reflexes. At autopsy, hypoplasia of kidneys and adrenal glands was found. There was no aqueductal stenosis or pulmonary hypoplasia. Chromosomes were apparently normal. These manifestations do not correspond to those of any recognized syndrome; therefore, this patient may represent a previously undefined syndrome.

Abnormalities, Multiple↗
PubMed1997

Goldenhar complex: a further case with uncommon associated anomalies.

We report on a further case of Goldenhar complex with uncommon and clinically remarkable associated anomalies. This additional case increases the number of observations and descriptions of patients with "expanded Goldenhar complex." Pathogenetic aspects are discussed.

Abnormalities, Multiple↗
PubMed1997

Brain anomalies, retardation of mentality and growth, ectodermal dysplasia, skeletal malformations, Hirschsprung disease, ear deformity and deafness, eye hypoplasia, cleft palate, cryptorchidism, and kidney dysplasia/hypoplasia (BRESEK/BRESHECK): new X-linked syndrome?

Two half brothers (maternally related) had a similar syndrome of microhydrocephaly in both brothers and dilatation of the spinal canal with fusion of thalami in one brother. Primordial growth delay was noted in both brothers, with severe mental retardation in the surviving brother. Both had ectodermal dysplasia with scaling, hyperkeratosis, and generalized alopecia, but normal sweat and sebaceous glands. Skeletal anomalies included hemivertebrae with abnormal segmentation in one and scoliosis with polydactyly in the other. Ears were apparently low set, large, and protruding, with mixed hearing loss in the brother who survived. Eye anomalies included maldevelopment of one eye in Patient 1 and small optic nerves more noticeable on one side in Patient 2. Both had cryptorchidism and dysplastic/hypoplastic kidneys of varying severity that resulted in the early postnatal death of one sib. Manifestations present in only one or the other sib included submucous cleft palate, aganglionosis of the rectum and colon, agenesis of one testicle, and single umbilical artery. This syndrome has not been described previously and may be due to an X-linked mutation. The acronym BRESEK reflects the common findings, whereas BRESHECK denotes all manifestations of both patients: brain, retardation, ectodermal dysplasia, skeletal deformities, Hirschsprung disease, ear/eye anomalies, cleft palate/cryptorchidism, and kidney dysplasia/hypoplasia. In addition to an X-linked mutation, a contiguous gene deletion or maternal mosaicism of an autosomal dominant gene must be considered.

Abnormalities, Multiple↗
PubMed1997

Germline mutations in the PTEN/MMAC1 gene in patients with Cowden disease.

Cowden disease, also known as multiple hamartoma syndrome, is an autosomal dominant cancer syndrome with a high risk of breast and thyroid cancer. The gene involved has been localized to chromosome 10q22-23. Recently, the tumour suppressor gene PTEN/MMAC1, encoding a putative protein tyrosine or dual-specificity phosphatase, was cloned from that region and three mutations were detected in patients with Cowden disease. We confirmed that the PTEN/MMAC1 gene is indeed the gene for Cowden disease by a refined localization of the gene to the interval between D10S1761 and D10S541, which contains the PTEN/MMAC1 gene and, by mutation analysis in eight unrelated familial and 11 sporadic patients with Cowden disease. Eight different mutations were detected in various regions of the PTEN/MMAC1 gene. One mutation was detected twice. All detected changes in the gene can be predicted to have a very deleterious effect on the putative protein. Five of the nine patients have a mutation in exon 5 coding for the putative active site and flanking amino acids. Evaluation of the clinical data of the patients in which a mutation could be detected gives no clear indications for a correlation between the genotype and phenotype. In 10 patients no mutation could be detected so far. In support of the linkage data, no evidence has emerged from the phenotype of these patients suggestive for genetic heterogeneity.

Adult↗
PubMed1996

Osteoglophonic dysplasia: review and further delineation of the syndrome.

We report on a boy with clinical and radiologic findings of osteoglophonic dysplasia. He had craniostenosis, "bizarre," expansile cystic lesions in the diaphyses, delayed tooth eruption, and progressive rib expansion typical of the syndrome. Initially delayed psychomotor development with later normal intelligence, early feeding and breathing difficulty, and speech delay are also characteristic of the disorder. Manifestations, not previously reported in osteoglophonic dysplasia, present in the propositus are spontaneous fractures resulting in pseudoarthroses through cystic and dysplastic foci in his proximal femoral shafts and right humerus, pretibial dimples, hypospadias, marked rib expansion, and absence of significant vertebral abnormality. These findings expand the spectrum of osteoglophonic dysplasia.

Bone Diseases, Developmental↗
PubMed1996

Blepharo-cheilo-dontic (BCD) syndrome.

Patients with the autosomal dominant ble-pharo-cheilo-dontic (BCD) syndrome have ectropion of lower eyelids, distichiasis of upper eyelids, euryblepharon, bilaterally cleft lip/palate, oligodontia, and conical crown form. Initially known under the eponym "Elschnig syndrome" (1912), BCD syndrome has been described in binary, ternary, and quaternary combination. There is overlap with the syndrome reported by Martínez et al. [1987], postaxial acrofacial dysostosis (Miller syndrome, Genée-Wiedemann syndrome), and a syndrome reported briefly by Warburg.

Child↗
PubMed1996

Confirmation of the Yemenite (Warburg) deaf-blind hypopigmentation syndrome.

The Yemenite deaf-blind hypopigmentation syndrome is a rare disorder characterized by severe early hearing loss, microcornea and colobomata, and cutaneous pigmentation abnormalities. A girl with similar skin symptoms and hearing loss, but no microcornea or colobomata is described and compared to other reported patients.

Child↗
PubMed1996

Weill-Marchesani syndrome--possible linkage of the autosomal dominant form to 15q21.1.

Weill-Marchesani syndrome comprises short stature, brachydactyly, microspherophakia, glaucoma, and ectopia lentis is regarded as an autosomal recessive trait (McKusick 277600). We present two families each with affected individuals in 3 generations demonstrating autosomal dominant inheritance of Weill-Marchesani syndrome. Linkage analysis in these 2 families suggests a gene for Weill-Marchesani syndrome maps to 15q21.1. The dislocated lenses and connective tissue disorder in these families suggests that fibrillin-1 and microfibril-associated protein 1, which both map to 15q21.1, are candidate genes for Weill-Marchesani syndrome. Immunohistochemistry staining of skin sections from family 1 showed an apparent decrease in fibrillin staining compared to control individuals.

Abnormalities, Multiple↗
PubMed1996

Oculo-facio-cardio-dental (OFCD) syndrome.

Oculo-facio-cardio-dental syndrome consists of (1) eye anomalies: congenital cataract and microphthalmia, or secondary glaucoma, (2) facial abnormalities: (long narrow face, high nasal bridge, pointed nose with cartilages separated at the tip, cleft palate, or submucous cleft palate, (3) cardiac anomalies: atrial septal defect (ASD), ventricular septal defect (VSD), or floppy mitral valve; and (4) dental abnormalities: canine radiculomegaly, delayed dentition, oligodontia, persistent primary teeth, or variable root length. Other less common findings are: sensorineural hearing loss, septate vagina, and syndactyly of toes 2-3. Inheritance may be an X-linked dominant trait, lethal in the male.

Adult↗