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Merrill D Benson

Publications and source records attributed to Merrill D Benson.

28 records · Page 2Linked to original sources
PubMed2003

Hereditary systemic amyloidosis associated with a new apolipoprotein AII stop codon mutation Stop78Arg.

UNLABELLED: Hereditary systemic amyloidosis associated with a new apolipoprotein AII stop codon mutation Stop78Arg. BACKGROUND: Mutations in the gene for apolipoprotein AII (apoAII) have recently been found to cause hereditary renal amyloidosis. In each case amyloid deposition has been associated with a peptide extension at the carboxyl-terminus of apoAII, the result of mutations in the normal stop codon. METHODS: A Caucasian man who has had progressive renal dysfunction since age of 34 was found to have amyloidosis on renal biopsy at age 56. Echocardiogram showed mild intraventricular septal thickness and technetium-99m (99mTc)-pyrophosphate scintigraphy demonstrated uptake by cardiac muscle consistent with amyloid deposition in the myocardium. His father died of renal failure and his paternal half brother has renal dysfunction. RESULTS: DNA sequencing of the apoAII gene in the proband showed a T to C transition at the first position of the stop codon indicating replacement of the stop codon by l-arginine (Arg) at residue 78. Western analysis of the proband's plasma under reducing conditions using anti-apoAII revealed an extra band at approximately 10 kD in addition to the normal apoAII band at 8 kD. Western analysis of solubilized amyloid fibrils isolated from rectal biopsy tissue contained only the variant apoAII. CONCLUSION: These results indicate that the proband's amyloid fibrils are derived from apoAII and the amyloidogenesis is linked to the peptide extension at the carboxyl-terminus of variant apoAII. Of particular interest is that this novel apoAII variant may cause amyloid cardiomyopathy in addition to renal amyloid.

Amino Acid Sequence↗
PubMed2003

A novel lysozyme mutation Phe57Ile associated with hereditary renal amyloidosis.

BACKGROUND: Variant forms of lysozyme, a ubiquitous bacteriolytic enzyme, are known to lead to hereditary non-neuropathic renal amyloidosis and, so far, three different mutations of the lysozyme gene have been reported. In this study, we report a novel lysozyme variant, Phe57Ile, associated with renal amyloidosis in three patients in one Italian Canadian family. METHODS: The proband was a 52-year-old woman who developed renal failure at the age of 42 years. Renal biopsy demonstrated replacement of glomeruli by amyloid. Her younger sister and her younger daughter who underwent renal transplantation also had renal amyloidosis. The proband's older daughter and her niece were in good health. To elucidate pathogenesis of this hereditary renal amyloidosis, DNA analyses of the lysozyme gene, including single strand confirmation polymorphism, direct DNA sequence, and restriction fragment length polymorphism analyses, were performed. RESULTS: DNA analyses of the lysozyme gene revealed a T to A transversion at the first position of codon 57 of the lysozyme gene in the proband, her sister, and her affected and unaffected daughters, indicating a replacement of Phe by Ile at residue 57. In addition, DNA sequencing demonstrated a C to A transversion at the second position of codon 70, denoting a replacement of Thr by Asn at residue 70, in the proband's sister and her niece. Thus, the proband's sister is compound heterozygous for the Phe57Ile and Thr70Asn alleles. CONCLUSION: Distinctive clinical features in patients of this family are nephropathy due to renal amyloidosis. Our results indicate that the novel lysozyme variant Phe57Ile is associated with renal amyloidosis in this family. From our results, a clear relation between the Thr70Asn polymorphism and renal amyloidosis could not be demonstrated.

Amyloidosis↗
PubMed2003

An allele of serum amyloid A1 associated with amyloidosis in both Japanese and Caucasians.

Serum amyloid A1 (SAA1), one of the two isotypes of acute phase SAA, is the predominant precursor to amyloid A (AA) protein, the chief constituent of fibrillar deposits in reactive (AA) amyloidosis. Prolonged hyperexpression of SAA protein accompanying chronic inflammation is critical to, but seems not to be sufficient for, the development of AA amyloidosis. Several previous studies have investigated the possibility of linkage between SAA1 exon 3 polymorphisms and susceptibility to amyloidosis. While the SAA1.1 allele was found to have a negative association with amylodosis in Japanese subjects, it showed a positive association in Caucasians. Moriguchi and colleagues recently showed that a single nucleotide polymorphism (SNP) at position -13 in the SAA1 5' flanking region was more strongly associated with amyloidosis than was the exon 3 polymorphism. To test whether this SNP may be an amyloidogenic factor common to Japanese and Caucasians, we have analyzed the SAA1 gene in amyloid and non-amyloid patients of both ethnic groups for the presence of T or C at position -13 and for exon 3 polymorphisms (SAA1.1, 1.3 or 1.5). The frequency of the -13T allele was 0.708 and 0.521 in Japanese rheumatoid arthritis patients with and patients without AA amyloidosis, respectively, and 0.536 and 0.196 in American Caucasian patients with AA amyloidosis and control subjects, respectively. In Caucasians, the -13T allele had a stronger association with amyloidosis than did the SAA1.1 allele. These findings suggest that -13T is a genetic background for AA amyloidosis in both Japanese and Caucasians and the difference in prevalence of AA amyloidosis in the two ethnic groups may be due, at least in part, to a difference in the frequency of the -13T SAA1 allele.

Alleles↗
PubMed2003

A transthyretin mutation (Tyr78Phe) associated with peripheral neuropathy, carpal tunnel syndrome and skin amyloidosis.

BACKGROUND: More than 80 transthyretin (TTR) mutations have been described, most associated with amyloidosis. Peripheral neuropathy is the most common clinical presentation in TTR amyloidosis although the carpal tunnel syndrome (CTS) may be the first symptom and skin can be involved, as transthyretin amyloidosis is a systemic disease. CASE REPORT: The 78 year-old proband, belonging to a French family of Italian origin, presented with a 5 year history of peripheral neuropathy in the lower extremities. However, 15 years earlier he had had surgery for bilateral CTS. Amyloidosis was diagnosed on salivary gland and skin biopsies. Immunohistochemistry on skin biopsy was positive using anti-TTR. The proband has 10 siblings, 5 have CTS. METHODS: SSCP and direct sequencing of exons 2, 3, and 4 of the TTR gene were done on DNA from the proband and his brother who had had CTS. To confirm the mutation a PCR-IMRA was done. RESULTS: SSCP analysis of TTR exons 2, 3, and 4 did not suggest a mutation. Sequence analysis of TTR exon 3 revealed heterozygosity in both subjects for a single basepair transversion from A to T in codon 78 (TAC-->TTC) indicating a tyrosine to phenylalanine change. The mutation was confirmed by PCR-IMRA. CONCLUSION: This TTR mutation (Tyr78Phe) is associated with peripheral neuropathy, carpal tunnel syndrome and skin amyloidosis. It is also associated with late onset of the disease.

Aged↗
PubMed2003

Renal transplantation for apolipoprotein AII amyloidosis.

Apolipoprotein AII (ApoAII) amyloidosis, first reported in 2001 in a family with renal amyloidosis, is associated with mutations in the stop codon of the apolipoprotein AII gene resulting in a carboxyl terminal peptide extension of 21 amino acid residues in the protein. Since death from this form of amyloidosis is due to renal failure, kidney dialysis and renal transplantation are presently the only two therapeutic options. We report the case of a Caucasian man who developed proteinuria in his late 20's, had renal biopsy at the age of 33 which gave the diagnosis of renal amyloidosis, and required continuous ambulatory peritoneal dialysis by age 45. He received a cadaver renal transplant at age 47 and has maintained stable renal function for nine years without other evidence for organ system dysfunction from amyloidosis. Laboratory studies confirmed persistence of the ApoAII variant in the patient's plasma in addition to the normal ApoAII protein. This is in agreement with the DNA analysis which showed the patient to be heterozygous for the ApoAII stop78Gly mutation. These results indicate that renal transplantation is an effective therapy for apolipoprotein AII amyloidosis since recurrence of amyloid in the graft and progression of other organ involvement may be very slow.

Adult↗
PubMed2002

Rapidly progressive amyloid polyneuropathy associated with a novel variant transthyretin serine 25.

We report a 52-year-old woman with a novel transthyretin (TTR) variant serine replacing alanine at residue 25 [Ala25Ser (Serine 25)], who showed a unique clinical picture with a relatively acute onset neuropathy within a few days of an influenza vaccination, progressing to a severe degree within 2 years. Sural nerve biopsy revealed amyloid deposition in the endoneurium. Sequencing of the proband's DNA revealed a G to T transversion at the first position of codon 25 of TTR gene. DNA analysis of this family showed the same mutation in her older sister and a niece, but her parents did not have the mutation. Haplotype analysis revealed the mutation to be clearly linked to haplotype III allele inherited from the proband's father. These results indicate this novel Serine 25 mutation originated in the paternal germline mosaicism. It is possible that the vaccination had an influence on the unique clinical picture, but this remains uncertain.

Amino Acid Sequence↗
PubMed2002

Laboratory assessment of transthyretin amyloidosis.

Mutations in transthyretin (TTR) are the most common cause of autosomal dominant systemic amyloidosis. To date, more than 80 TTR mutations have been associated with amyloidosis in humans. A high prevalence of some mutations like Val122Ile which is identified in 3% of African Americans indicates the necessity of thorough investigation of patients suspected of having, or to be at risk of developing, TTR amyloidosis. Laboratory tests available for evaluation of TTR amyloidosis include both DNA and protein assays. In the case of a known mutation DNA analysis is realized by restriction fragment length polymorphism (RFLP), polymerase chain reaction-induced mutation restriction analysis (PCR-IMRA), single strand confirmation polymorpism (SSCP) or nucleotide sequencing. SSCP, PCR-non-isotopic RNAse cleavage assay (NIRCA) or nucleotide sequencing are used to identify an unknown mutation. At the protein level, two techniques are used, isoelectric focusing and mass spectrometry, in both cases (known or unknown mutation). The identification of a previously unknown mutation requires a combination of clinical, pathological and molecular studies.

Amyloidosis, Familial↗
PubMed2002

Transthyretin amyloidosis associated with a novel variant (Trp41Leu) presenting with vitreous opacities.

We report a 45-year-old woman with a new transthyretin (TTR) variant, substitution of leucine for tryptophan at residue 41, who has showed vitreous opacities without any other visceral organ involvement since age of 42. Congo red staining of vitrectomy specimens revealed that the vitreous fluid contained amyloid fibrils, which were strongly positive for immunohistochemical staining using anti-human TTR antiserum. DNA analysis of the TTR gene showed a G to T transversion at the second nucleotide of codon 41, indicating a replacement of tryptophan (TGG) by leucine (TTG). These results indicate that the patient's vitreous amyloid is associated with this novel TTR mutation.

Amyloidosis↗
PubMed2002

A new transthyretin variant Leu55Gln in a patient with systemic amyloidosis.

We report a 40-year-old woman with a new transthyretin (TTR) variant, glutamine replacing leucine at residue 55 (Leu55Gln), who showed progressive somatic and autonomic neuropathy, glaucoma, and vitreous opacities. Symptoms of glaucoma appeared prior to the onset of the neuropathy. Sural nerve biopsy revealed amyloid deposition in the endoneurium, and immunohistochemical analysis was positive with anti-human TTR. Sequencing of the patient's DNA revealed the substitution of A for T at the second position of codon 55 of the TTR gene indicating an amino acid change from leucine to glutamine.

Amyloidosis↗