A novel presenilin 1 mutation (L174 M) in a large Cuban family with early onset Alzheimer disease.

We studied a Cuban family with presenile dementia (autosomal dominant) consisting of 281 members within six generations, the proband descended from a Spanish founder. Mean age at onset was 59 years of age. Memory impairment was the main symptom in all patients, additionally, ischemic episodes were described in 4 (n = 18) patients. Neuropathological examination of brain material (1 patient) revealed neuronal loss, amyloid plaques, and neurofibrillary tangles. Thirty DNA samples were genotyped (regions on chromosome 1, 3, 10, 12, 14, 17, 19, 20, and 21). A maximum Lod score of 3.79 at theta = 0 was obtained for marker D14S43, located in a 9-cM interval in which all patients shared the same haplotype. Sequencing of the PSEN1 gene revealed a heterozygous base substitution, C520A (exon 6), which is predicted to cause an amino acid change from leucine to methionine in the TMIII of the presenilin 1 protein. The mutation was found to co-segregate with the disease phenotype and the associated disease haplotype. The C --> A change was not observed in 80 control chromosomes from the Cuban population. Leucine at position 174 is highly conserved among species and is identical in presenilin 1 and presenilin 2 proteins. We propose the L174 M mutation might lead to an abnormal N-terminal and probably C-terminal fragments and malfunction of the protein complex. In conclusion, we found a novel PSEN1 mutation in a large family with clinical and pathological diagnosis of early onset familial Alzheimer disease, which may be relevant for other Hispanic populations.

[Cystic adenoid carcinoma of the prostate. Report of a case]. / Carcinoma adenoideo quístico de la próstata. Presentación de un caso.

OBJECTIVES: To describe a 41-year-old, white, male patient with a previous history of rectal pain. He was diagnosed as having a prostatic tumor and was treated with antiandrogens and irradiation, which temporarily achieved temporary symptomatic relief. When the symptoms reappeared, the patient consulted at our hospital. A multinodular tumor was detected in the rectum. Transrectal ultrasound-guided biopsy disclosed adenoid cystic carcinoma of the prostate or adjacent structures. METHODS/RESULTS: The characteristics of the lesion prompted tumor excision alone. Since the integrity of the rectal and prostatic urethra could not be preserved, a recto-urethral fistula was done, which was subsequently closed via the transrectal approach. The clinical characteristics of the tumor and the surgical procedure performed required treatment with an antitumoral immunomodulator (recombinant a-interferon) for one year. CONCLUSIONS: One and a half years postoperatively, no signs of tumor recurrence or distant metastasis have been observed. To our knowledge, this is the seventh case reported in the world literature and the first in the Spanish literature.

[Primary diffuse leptomeningeal gliomatosis. Presentation of one case]. / Gliomatosis leptomeníngea difusa primaria: presentación de un caso.

A twenty-four-year-old woman presented with asthenia, anorexia and weight los associated with headache, neck ache, lumbo-sacral pain, flaccid quadriparous, bilaterally diminished vision and sphincter disorders. On computerized axial tomography of the skull, only slight signs of ventricular dilatation were seen. Cytochemical study of the cerebro-spinal fluid showed a marked increase in protein and there was a raised erythrocyte sedimentation rate. The patient was treated with steroids in view of the possibility of vasculitis or a demyelinating disorder. However the disease worsened and she died four months after onset of the disorder. Neuro-pathological study showed tumour infiltration of the leptomeninges of the base of both cerebral hemispheres, cerebellum and spinal medulla. The optic nerves, chiasma and spinal nerve roots were also infiltrated with neoplastic cells. No intraparenchymatous tumour was found. The neuropathological findings were compatible with primary diffuse leptomeningeal gliomatosis.