Association of interleukin-1 gene polymorphisms with sudden sensorineural hearing loss and Ménière's disease

Sudden sensorineural hearing loss (SSNHL) and Ménière's disease are the most common inner ear diseases in which the causes are unknown. As recent magnetic resonance imaging has demonstrated disruption of the blood-labyrinth barrier in these inner ear diseases, inflammatory reaction associated with increased permeability of the blood vessels may be involved. The genotypes of interleukin 1A (IL1A) (-889C/T; rs1800587) and interleukin 1B (IL1B) (-511C/T; rs16944) were determined using an allele-specific primer-polymerase chain reaction method in 72 patients with SSNHL, 68 patients with Ménière's disease, and 2202 control subjects living almost in the same area as the patients. A significantly higher prevalence of the IL1A-889T allele was observed in SSNHL and Ménière's disease compared with controls, although no significant difference in distribution of IL1B-511C/T genotypes was observed between the patients and controls. Adjusted odd ratios for SSNHL and Ménière's disease risks in the -889TT genotypes were 25.89 (95% confidence interval (CI) 12.19-54.98) and 18.20 (95% CI 7.80-42.46), respectively, after age and gender were taken as moderator variables. Our results suggested that IL1A is closely associated with susceptibility of SSNHL and Ménière's disease.     

Diagnostic dilemma: a young woman with Fabry disease symptoms, no family history, and a "sequencing cryptic" α-galactosidase a large deletion

Fabry disease, an X-linked lysosomal storage disorder, results from the deficient activity of α-galactosidase A (α-Gal A). In affected males, the clinical diagnosis is confirmed by the markedly decreased α-Gal A activity. However, in female heterozygotes, the α-Gal A activity can range from low to normal due to random X-chromosomal inactivation, and diagnostic confirmation requires identification of the family's α-Gal A gene mutation. In a young female who had occasional acroparesthesias, corneal opacities, and 15 to 50% of the lower limit of normal leukocyte α-Gal A activity, α-Gal A sequencing in two expert laboratories did not identify a confirmatory mutation, presenting a diagnostic dilemma. A renal biopsy proved diagnostic and renewed efforts to detect an α-Gal A mutation. Subsequent gene dosage analyses identified a large α-Gal A deletion confirming her heterozygosity, and she was started on enzyme replacement therapy. Thus, gene dosage analyses can detect large deletions (> 50 bp) in suspect heterozygotes for X-linked and autosomal dominant diseases that are “sequencing cryptic,” resolving molecular diagnostic dilemmas.     

A WNT4 mutation associated with Müllerian-duct regression and virilization in a 46,XX woman

WNT4, a secreted protein that suppresses male sexual differentiation, is thought to repress the biosynthesis of gonadal androgen in female mammals. An 18-year-old woman presented with primary amenorrhea and an absence of müllerian-derived structures, unilateral renal agenesis, and clinical signs of androgen excess--a phenotype resembling the Mayer-Rokitansky-Küster-Hauser syndrome and remarkably similar to that of female Wnt4-knockout mice. A genetic evaluation revealed a loss-of-function mutation in the WNT4 gene. WNT4 appears to be important in the development and maintenance of the female phenotype in women, by means of the regulation of müllerian-duct formation and control of ovarian steroidogenesis.     

Superficial gastric carcinoma developed on localized hypertrophic lymphocytic gastritis: a variant of localized Ménétrier's disease?

Ménétrier's disease is a rare premalignant condition that usually involves the entire stomach. Only few cases of localized disease have been reported, rarely with cancer. Lymphocytic gastritis is a newly described entity that may share a common pathogenesis with Ménétrier's disease. The authors report the case of a 62 year old woman with known liver cirrhosis in whom endoscopic examination of the stomach showed an antral tumor. Examination of the surgical specimen showed a superficial gastric adenocarcinoma developed on an hypertrophic gastropathy with both Ménétrier's disease and lymphocytic gastritis features. This observation strengthens the hypothesis of a common mechanism between Ménétrier's disease and lymphocytic gastritis, which may be part of the same disease spectrum. This disease could also correspond to the "hypertrophic lymphocytic gastritis" recently described.     

Reduplication cyst of appendix with mucinous carcinoma and Müllerian metaplasia: a case report

This report describes a case of mucinous carcinoma and Müllerian metaplasia arising within an appendiceal duplication cyst found incidentally during an emergency Caesarian section. Intestinal duplication cysts are rare and although there are occasional reports of malignant transformation, this is the first case where Müllerian metaplasia was found concurrently with a malignancy. There was no previous history of endometriosis and no other abnormalities were found at surgery. Treatment included surgical excision. The patient is alive and well two years after removal of the cyst.     

Complex Müllerian malformation: report of a case with a hypoplastic non-cavitated uterus and two rudimentary horns

Various classifications have been used for congenital anomalies of the Müllerian system. We report a case of a previously unknown anomaly of the uterus, and propose its possible embryological causes. The patient presented with primary amenorrhoea and infertility, and during laparoscopy three distinct uterine horns were observed. The tubes were connected to the two most lateral horns, each juxtaposed to a normal ovary. The middle horn had a seemingly normal attachment to the right uterosacral ligament, whereas its attachment to the left uterosacral ligament appeared attenuated and less normal. Furthermore, the right horn was immediately attached to the middle horn, whereas the left horn was, like its ipsilateral uterosacral ligament, attached to the middle horn by a more attenuated, stretched fibrous bridge. Only the middle horn, with its uterosacral ligaments, had an attached, although obstructed, cervix. Ultrasonographic examination revealed no endometrium echogeneity in any of these uterine bulbs. No etiologic factors were noted in the patient's history; her mother denied known ingestion of estrogens or other drugs while carrying her daughter. The pathogenesis of this anomaly cannot be clearly defined, but may involve sequential embryological errors of duplication of the Müllerian tracts, failure of fusion of each set of the Müllerian tracts with expected failed canalization of each tract and, finally, agenesis of the medial horn of the left duplicated tracts.     

Escherichia coli ehl1 gene-positive serotype O18ac:H31 associated with an outbreak of diarrhea in a neonatal nursery in Neuquén City, Argentina

Between 9 October and 12 November 1996, an outbreak of bloody diarrhea occurred in the neonatal nursery ward of the Policlínico Neuquén, in Neuquén, a city in the southwestern region of Argentina. Seven patients of the intermediate care unit were affected. Isolates of Escherichia coli O18ac:H31 that were non-lactose and -sorbitol fermenting were recovered from outbreak cases. Although the strains were negative for a number of virulence factors typically found in diarrheagenic groups of E. coli, all isolates from the present neonatal outbreak possessed the enterohemolysin gene, ehl1. All isolates showed resistance to the antibiotics ampicillin and chloramphenicol. These isolates showed a low adherence property in HeLa cells without any recognizable pattern. In order to evaluate the outbreak dissemination in the neonatology ward, a prevalence study was conducted on 13 November. Stool specimens were obtained from 16 neonates hospitalized in the sector and from 33 medical staff members. E. coli isolates with identical biochemical characteristics of the outbreak strain were recovered from 11 of 16 inpatients and from 4 of 33 staff members during the prevalence study. A total of 15 E. coli strains recovered both from the outbreak and the prevalence study were processed by random amplified polymorphic DNA (RAPD)-PCR and pulsed-field gel electrophoresis (PFGE). By RAPD-PCR 14 of 15 strains showed patterns with 85 to 100% similarity, and by PFGE these strains were identical, each showing a unique pattern with 15 bands between 40 and 400 kb. One strain isolated from a nurse during the prevalence study presented a pattern not related to the others, and this was characterized as E. coli O81:HNM resistant to ampicillin only and negative for all the virulence factors studied. This outbreak occurred despite strict regulations in place to prevent cross-infection in the hospital. Postoutbreak prevalence studies were performed weekly thereafter without detecting new cases.     

Congenital hypertrichosis, cardiomegaly, and osteochondrodysplasia (Cantú syndrome): a new case with unusual radiological findings

We report on a new case of a syndrome first described by Cantú et al. [1982: Hum Genet 60:36-41] comprising congenital hypertrichosis, "coarse" facial appearance, and mild osteochondrodysplasia. Our case has some unusual radiological findings, namely proximal and distal megaepiphyses of long bones and advanced bone age.     

Genetic diversity of HLA system in two populations from Yucatán,Mexico: Mérida and rural Yucatán

We studied HLA class I (HLA-A, -B) and class II (HLA-DRB1, -DQB1) alleles by PCR-SSP based typing in 324 Mexicans from the state of Yucatán living in the city of Mérida (N = 192) and rural communities (N = 132), to obtain information regarding allelic and haplotypic frequencies. We found that the most frequent haplotypes in the state of Yucatán include 16 Native American and one European haplotype. Admixture estimates revealed that the main genetic components in Yucatán are Native American (81.54 ± 4.99% by ML; 62.92% of Native American haplotypes) and European (11.50 ± 15.43% by ML; 23.26% of European haplotypes), and a less prominent African genetic component (6.96 ± 10.47% by ML; 5.93% of African haplotypes).     

A Scottish family with Bazex-Dupré-Christol syndrome: follicular atrophoderma, congenital hypotrichosis, and basal cell carcinoma.

Bazex-Dupre-Christol syndrome (BDCS) is an X linked dominant disorder of the hair follicle characterised by follicular atrophoderma, multiple basal cell carcinomas, hypotrichosis, milia, and localised hypohidrosis. Follicular atrophoderma (FA) are follicular funnel shaped depressions, "ice pick marks", seen most commonly on the dorsum of the hands. We describe the first known Scottish family with this syndrome, five affected members spanning three generations. They have hypohidrosis confined to the face, coarse hair, dry skin, milia, and follicular atrophoderma. All the adults have a history of multiple basal cell carcinomas. None of them has any skeletal feature suggestive of Gorlin's syndrome. The clinical features, skin histology, and scanning electron microscopic (SEM) examination of the hair are described and illustrated. The features are compared with 15 previous reports of BDCS and four reports in which this is a possible diagnosis are also reviewed. BDCS should be considered as a differential diagnosis in patients with early onset or familial basal cell carcinomas.     

Family with branchial arch anomalies,hearing loss,ear and commissural lip pits,and rib anomalies. A new autosomal recessive condition: Branchio-oto-costal syndrome?

We report on a family in which 3 sibs were affected with conductive deafness, bilateral preauricular and commissural lip pits, monolateral branchial fistula, and rib anomalies. On the basis of parental consanguinity, lack of clinical variability and affected subjects of both sexes, this condition seems to be inherited as an autosomal recessive trait. We suggest that these findings comprise a new autosomal recessive entity of branchial, auricular and costal anomalies, for which we suggest the acronym BOC (branchiooto-costal) syndrome. Am. J. Med. Genet. 68:91–93, 1997 © 1997 Wiley-Liss, Inc.