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PubMed1986

Rare variants of Hodgkin's disease of the thymus: report of two cases and proposal for effective clinical management.

We treated two patients with rare variants of Hodgkin's disease of the thymus. One was a 17-year-old girl with a thymoma-like shadow on the chest X-rays, an increased erythrocyte sedimentation rate and an elevated eosinophil count. Pathologically, a mixed cellularity variant of thymus Hodgkin's disease was evident. The other patient was 22-year-old girl with evidence of mediastinal tumor on the chest X-rays. Pathological examination revealed Hodgkin's disease of the lymphocyte predominance variety. She also had Von der Haeve syndrome. In both cases, Hodgkin's disease was suspected by scintiscanning, using three kinds of radioisotope, 201Thallium-chloride, 67Garium-citrate and 75Selenomethionine. Radical excision of the lesion plus preoperative and postoperative irradiations were carried out. Both are well 6 and 5 years after the treatment, respectively. We propose a new diagnostic procedure and a method of treatment for such patients.

Adolescent↗
PubMed2006

Solid serous adenoma of the pancreas: a rare variant within the family of pancreatic serous cystic neoplasms.

We report the third case of a solid serous adenoma of the pancreas, a rare variant of tumor within the family of pancreatic serous cystic neoplasms. This asymptomatic tumor presented in a 66-year-old man during imaging for another problem. Computed tomography of the abdomen demonstrated a 3.5-cm hypervascular mass in the head of the pancreas. A pylorus preserving pancreaticoduodenectomy was performed. Histological examination demonstrated a neoplasm identical to a serous cystadenoma-glycogen-rich cuboidal or polygonal cells with finely granulated eosinophilic or clear cytoplasm. More often, the neoplasm contained solid areas and tubules but no microcysts. Periodic acid Schiff's-glycogen staining was positive in some cells, turning negative after diastase was applied. Immunostaining was positive for CK7, CK8, neuron specific enolase, and MUC6. The microscopic findings of a solid neoplasm of cuboidal cells rich in glycogen and the immunostaining listed associate this tumor with the previously 2 reported cases of solid serous adenoma. All 3 reported cases thus far have proven to be benign lesions by pathological examination. Because clinical follow-up is reported only in the present case, caution should be exercised in declaring the solid serous adenoma of the pancreas as a benign lesion.

Aged↗
PubMed2001

Chronic myeloid leukemia with a rare variant Philadelphia translocation: t(9;10;22)(q34;q22;q11).

We report a 59-year-old, male, chronic myeloid leukemia patient with a rare variant Philadelphia (Ph) translocation t(9;10;22)(q34;q22;q11). Fluorescence in situ hybridization with whole chromosome paints was used to confirm the cytogenetic findings. With a BCR/ABL-specific probe, the known rearrangement on the derivative chromosome 22 was found. The prognostic implications as well as the relevance of the additional breakpoint region 10q22 are discussed.

Chromosomes, Human, Pair 10↗
PubMed1994

Congenital complete absence (bilateral agenesis) of the diaphragm: a rare variant of congenital diaphragmatic hernia.

Although congenital diaphragmatic hernia is one of the most common congenital anomalies, complete bilateral absence of the diaphragm is a very rare variant, with six cases reported in the literature. A 1040 g black male infant was born at 27 weeks' gestation to a 28-year-old black woman with a history of minimal prenatal care and cocaine abuse during pregnancy. Apgar scores were 2/1/1/0/1 at 1, 5, 10, 15, and 20 minutes, respectively and efforts to resuscitate him were unsuccessful. He died at 2 1/2 hours of age. Autopsy showed complete absence of the diaphragm, pulmonary hypoplasia, and an atrial septal defect of the heart. Cytogenetic studies showed normal male karyotype. We suggest that decreased or interrupted blood supply to the developing diaphragm of this infant may have interrupted normal embryogenesis in the early developmental stages.

Abnormalities, Drug-Induced↗
PubMed1990

Genetic variation of alpha-2-HS-glycoprotein in the Kyushu district of Japan: description of three new rare variants.

The genetic polymorphism of alpha 2-HS-glycoprotein (AHSG) was studied in the Kyushu district of Japan using polyacrylamide gel isoelectric focusing, followed by immunoblotting. Three new rare variants were observed and designated AHSG*16, AHSG*17 and AHSG*18, tentatively. The frequencies of the polymorphic genes AHSG*1 and AHSG*2 were similar to those in other areas of Japan.

Fibronectins↗
PubMed2026

Investigating genetic susceptibility to concussion through rare variants in ion channel and neurotransmission genes.

Some individuals appear more susceptible to concussion or mild traumatic brain injury (mTBI) and the severity, range, and the persistence of post-concussion symptoms vary considerably between affected individuals. Genetic factors are likely to contribute to this variability. Symptomatic overlap of post-concussion syndrome with neurological conditions such as familial hemiplegic migraine (FHM) caused by rare pathogenic variants in ion channel and synapse protein genes, with high sensitivity to head trauma for some patients, suggests that variation in similar pathways may influence concussion susceptibility and recovery. To investigate this hypothesis, we performed whole exome sequencing in 93 unrelated individuals who had sustained a single or multiple concussions and examined rare protein-altering variants in FHM genes, other neuronal ion channel and transporter genes, and genes involved in neurotransmission. We identified 62 different rare missense variants across 24 genes in 59 participants (63%), with 26 individuals carrying 2 or more variants. The prevalence of specific likely damaging rare variants in the 16 ion channel-related genes that were identified was approximately fivefold higher than that observed from gnomAD population controls (Odds Ratio = 5.44, 95% CI [4.13,7.18], P < 0.0001). Notably, voltage-gated calcium and sodium channel genes, including SCN9A, together with neurotransmission-related genes such as SNCAIP, harboured multiple potentially deleterious variants. These findings suggest that rare deleterious variants in genes involved in ion homeostasis and neurotransmission may contribute to an individual's susceptibility to concussion or more severe post-concussion symptoms. This study provides a foundation for future genetic and functional investigations aimed at improving our understanding of concussion susceptibility and outcomes. Further validation in larger cohorts and mechanistic studies is warranted to determine their utility as biomarkers of concussion risk and prognosis.

Humans↗
PubMed1990

[Chorea mollis, a rare variant of chorea minor].

A 15-year-old boy was admitted at age 10 because of muscle weakness, choreatic involuntary movements, and a profound hypotonia. He was diagnosed as having chorea mollis, a rare variant of Sydenham's chorea. He made a full recovery and received prophylaxis with monthly injections of benzathinebenzyl penicillin for the next 5 years. Six months after discontinuation of the prophylaxis he had a recurrence. The choreatic movements were successfully treated with haloperidol. However, a hypotonia and mild psychiatric symptoms still persist one year later. The clinical course, observed in our patient, is in concordance with the results of recent studies, reporting, that a number of patients with Sydenham's chorea may be left with mild to moderate neurologic and psychiatric sequelae.

Adolescent↗
PubMed1984

Rare variant of complement C4 is seen in high frequency in patients with primary glomerulonephritis.

59 unselected patients with primary glomerulonephritis were phenotyped for alleles of the MHC-linked complement genes, C4A, C4B, and BF. A rare variant of the C4B locus, C4B*2.9, was found in 25% of these patients compared with only 2% of the normal population--a relative risk of 22.1 for glomerulonephritis in individuals with this variant. Subdivision of patients by histological classification of glomerulonephritis revealed a significant association of C4B*2.9 with the membranoproliferative form. There were no significant associations between primary glomerulonephritis or its subtypes and the other HLA markers tested.

Alleles↗
PubMed2024

Validating the splicing effect of rare variants in the SLC26A4 gene using minigene assay.

BACKGROUND: The SLC26A4 gene is the second most common cause of hereditary hearing loss in human. The aim of this study was to utilize the minigene assay in order to identify pathogenic variants of SLC26A4 associated with enlarged vestibular aqueduct (EVA) and hearing loss (HL) in two patients. METHODS: The patients were subjected to multiplex PCR amplification and next-generation sequencing of common deafness genes (including GJB2, SLC26A4, and MT-RNR1), then bioinformatics analysis was performed on the sequencing data to identify candidate pathogenic variants. Minigene experiments were conducted to determine the potential impact of the variants on splicing. RESULTS: Genetic testing revealed that the first patient carried compound heterozygous variants c.[1149&#x2009;+&#x2009;1G&#x2009;>&#x2009;A]; [919-2&#xa0;A&#x2009;>&#x2009;G] in the SLC26A4 gene, while the second patient carried compound heterozygous variants c.[2089&#x2009;+&#x2009;3&#xa0;A&#x2009;>&#x2009;T]; [919-2&#xa0;A&#x2009;>&#x2009;G] in the same gene. Minigene experiments demonstrated that both c.1149&#x2009;+&#x2009;1G&#x2009;>&#x2009;A and c.2089&#x2009;+&#x2009;3&#xa0;A&#x2009;>&#x2009;T affected mRNA splicing. According to the ACMG guidelines and the recommendations of the ClinGen Hearing Loss Expert Panel for ACMG variant interpretation, these variants were classified as "likely pathogenic". CONCLUSIONS: This study identified the molecular etiology of hearing loss in two patients with EVA and elucidated the impact of rare variants on splicing, thus contributing to the mutational spectrum of pathogenic variants in the SLC26A4 gene.

Humans↗
PubMed1987

A rare variant of common arterial trunk.

A 13 day old baby was admitted to hospital with multiple abnormalities, increasing cyanosis, and cardiac failure. Cardiac catheterisation was performed on the day of admission and he died shortly after the procedure. A rare variant of common arterial trunk, in which the pulmonary arteries arose directly from the underside of the aortic arch, was found at necropsy.

Humans↗
PubMed1998

Type I transforming growth factor beta receptor maps to 9q22 and exhibits a polymorphism and a rare variant within a polyalanine tract.

In a search for mutations of the type I transforming growth factor beta receptor (TbetaR-I), we mapped the gene to 9q22 and found a common polymorphism [TbetaR-I(6A)] and a rare variant [TbetaR-I(10A)] of TbetaR-I, causing an in-frame deletion of three alanines and an in-frame insertion of one alanine, respectively, in the receptor's extracellular domain. The biological relevance of the polymorphism TbetaR-I(6A) was investigated. When TbetaR-I(6A) was transiently transfected into TbetaR-I-deficient cells, the growth-inhibitory effects of transforming growth factor beta were restored. TbetaR-I(6A) and TbetaR-I(10A) frequency were assessed in 108 tumor samples and 80 nontumor samples from patients with a diagnosis of cancer, as well as in 118 normal blood donors of comparable ethnic composition. The frequency of TbetaR-I(6A) heterozygotes was fairly similar in normal blood donors (8%), in nontumor DNA of patients with a diagnosis of cancer (10%), and in tumor samples (14%). However, the frequency of TbetaR-I(6A) homozygotes among nontumor (4%) and tumor (8%) samples obtained from patients with a diagnosis of cancer was higher than that predicted by the Hardy-Weinberg law. The clinical and biological significance of TbetaR-I(6A) homozygosity needs to be further investigated.

Acute Disease↗
PubMed2005

A survey of haplotype variants at several disease candidate genes: the importance of rare variants for complex diseases.

BACKGROUND: The haplotype based association method offers a powerful approach to complex disease gene mapping. In this method, a few common haplotypes that account for the vast majority of chromosomes in the populations are usually examined for association with disease phenotypes. This brings us to a critical question of whether rare haplotypes play an important role in influencing disease susceptibility and thus should not be ignored in the design and execution of association studies. METHODS: To address this question we surveyed, in a large sample of 1873 white subjects, six candidate genes for osteoporosis (a common late onset bone disorder), which had 29 SNPs, an average marker density of 13 kb, and covered a total of 377 kb of the DNA sequence. RESULTS: Our empirical data demonstrated that two rare haplotypes of the parathyroid hormone (PTH)/PTH related peptide receptor type 1 and vitamin D receptor genes (PTHR1 and VDR) with frequencies of 1.1% and 2.9%, respectively, had significant effects on osteoporosis phenotypes (p = 4.2 x 10(-6) and p = 1.6 x 10(-4), respectively). Large phenotypic differences (4.0 approximately 5.0%) were observed between carriers of these rare haplotypes and non-carriers. Carriers of the two rare haplotypes showed quantitatively continuous variation in the population and were derived from a wide spectrum rather than from one extreme tail of the population phenotype distribution. CONCLUSIONS: These findings indicate that rare haplotypes/variants are important for disease susceptibility and cannot be ignored in genetics studies of complex diseases. The study has profound implications for association studies and applications of the HapMap project.

Apolipoproteins E↗
PubMed2006

Haemorrhagic polymorphic light eruption: two cases of a rare variant.

Polymorphic light eruption is a common photosensitivity disorder of unknown aetiology, that usually presents in the spring or summer months as an intermittent non-scarring, itchy erythematous, papulo-vesicular eruption. We present two cases of haemorrhagic polymorphic light eruption, a rare variant of this condition of which there are no case reports in the literature.

Adult↗
PubMed2006

Solitary intramuscular myxoma with monostotic fibrous dysplasia as a rare variant of Mazabraud's syndrome.

The rare coexistence of intramuscular myxoma (IM) and fibrous dysplasia (FD) is known as Mazabraud's syndrome. IM tends to occur multifocally and is associated most frequently with polyostotic FD in Mazabraud's syndrome. We present an extremely rare combination of a solitary IM and monostotic FD as a variant of Mazabraud's syndrome, and discuss the importance of recognizing this rare coexistence for appropriate management of the patient.

Biopsy↗
PubMed1983

Rare variant alleles in the light of the neutral theory.

Based on the neutral theory of molecular evolution and polymorphism, and particularly assuming "the model of infinite alleles," a method is proposed which enables us to estimate the fraction of selectively neutral alleles (denoted by Pneut) among newly arisen mutations. It makes use of data on the distribution of rare variant alleles in large samples together with information on the average heterozygosity. The formula proposed is Pneut = [He/(1-He)] [loge(2nq)/n alpha (x less than q)], where n alpha(x less than q) is the average number of rare alleles per locus whose frequency, x, is less than q; n is the average sample size used to count rare alleles; He is the average heterozygosity per locus; and q is a small preassigned number such as q = 0.01. The method was applied to observations on enzyme and other protein loci in plaice, humans (European and Amerindian), Japanese monkeys, and fruit flies. Estimates obtained for them range from 0.064 to 0.21 with the mean and standard error Pneut = 0.14 +/- 0.06. It was pointed out that these estimates are consistent with the corresponding estimate Pneut(Hb) = 0.14 obtained independently based on the neutral theory and using data on the evolutionary rate of nucleotide substitutions in globin pseudogenes together with those in the normal globins.

Alleles↗
PubMed1990

A rare variant of acinic cell carcinoma of the upper lip: a case report and review of the literature.

Acinic cell carcinomas of the lip are most uncommon. An exhaustive search of the Japanese- and English-language literature has revealed only 17 previously reported cases. One additional occurrence, a rare variant of this type of neoplasm, with mucous differentiation, that occurred in the upper lip of a 60-year-old man is described here. A brief review of the literature on this type of lip tumor is also given.

Carcinoma↗
PubMed1983

Transferrin: common and rare variants in italy. Evidence for the existence of the rare TfC6 among Caucasians.

The results of a large screening for the transferrin polymorphism in five different areas of Italy (3099 cases) are given. Frequencies of common types were similar to those of already known Caucasian populations. Among rare types TfB were more frequently observed than TfD. Evidence is given for the existence of the TfC6 allele in Caucasians. A family group analysis of some rare types was done.

Gene Frequency↗