Amyloidotic polyneuropathy in a Jewish family. Evidence for the genetic heterogeneity of the lower limb familial amyloidotic neuropathies.
Amyloidotic polyneuropathy in a Jewish family. Evidence for the genetic heterogeneity of the lower limb familial amyloidotic neuropathies.
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犹太家庭的淀粉样多发性神经病。
DOI：
10.1093/oxfordjournals.qjmed.a067851
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发表时间：
1985
期刊：
影响因子：
--
通讯作者：
M. Pras
中科院分区：
文献类型：
--
作者：
J. Gafni;B. Fischel;R. Reif;M. Yaron;M. Pras
第一例家族性淀粉样多发性神经病影响一个犹太家庭的报告。玻璃体混浊是其在父亲30岁和儿子25岁时的表现特征。严重的自主神经功能障碍和进行性周围神经病变，最初影响下肢不久。死亡，自杀的儿子，发生在七年和四年的疾病。他们的淀粉样蛋白包含三种蛋白质-前白蛋白的完整变体单体，甘氨酸取代苏氨酸作为残基49，以及在取代点切割的两种产物。下肢家族性淀粉样多发性神经病已记录在葡萄牙，瑞典和日本的许多家庭，偶尔在家庭的各种种族的股票。这种种族多样性促使人们考虑遗传异质性。遗传基础上的分化是预先阻止的，因为所有的家系都符合常染色体显性遗传，临床数据被观察者方差破坏，即使是关于玻璃体混浊。尽管如此，一个孤立的英国家庭是独特的，在顽固性消化性溃疡，白内障，耳聋和肾脏疾病的频繁发生，而不是归因于淀粉样变性和一个显着的优势，男性患病。在生物化学上，单体前白蛋白已被电泳和免疫学技术证明是从葡萄牙、日本和瑞典患者中分离的淀粉样蛋白的单一蛋白组分。日本淀粉样蛋白的变体前白蛋白的特征在于蛋氨酸取代缬氨酸作为残基30，并且与受影响的瑞典人血浆中发现的相同（但尚未在淀粉样蛋白中发现）。这些有限的数据表明：（a）从前白蛋白衍生的淀粉样蛋白是下肢家族性淀粉样神经病的生物化学共同点，而与患者的种族无关;（B）在种族多样性反映遗传异质性的程度上，这将在淀粉样蛋白中得到证实（并且希望在血浆中）作为通过不同的单个氨基酸取代区分的实体特异性变体前白蛋白单体;（三）基于临床及生化的理由，家族性下肢淀粉样神经病包括最少三种遗传因素。在上肢和面部形式的家族性淀粉样多发性神经病首先记录在瑞士和芬兰人分别，在他们的神经系统疾病和眼部病变的模式的差异可能是由于他们的淀粉样蛋白来源于蛋白质以外的前白蛋白。
The first instance of familial amyloidotic polyneuropathy affecting a Jewish family is reported. Vitreous opacities were its presenting feature in the father at age 30 and the son at 25. Severe autonomic dysfunction and progressive peripheral neuropathy affecting initially the lower extremities soon followed. Death, suicidal in the son, occurred after seven and four years of illness. Their amyloid contained three proteins-an entire variant monomer of prealbumin, glycine replacing threonine as residue 49, and both products of its cleavage at the point of substitution. Lower limb familial amyloidotic polyneuropathy has been recorded in many families in Portugal, Sweden and Japan and occasionally in families of various ethnic stocks. This ethnic diversity prompts consideration of genetic heterogeneity. Differentiation on a genetic basis is forestalled since all pedigrees are compatible with autosomal dominant transmission and clinical data are marred by observer variance, even regarding vitreous opacities. Notwithstanding, an isolated British family is unique in the frequent occurrence of intractable peptic ulceration, cataracts, deafness and renal disease not attributable to amyloidosis and a striking predominance of males afflicted. Biochemically, monomeric prealbumin has been demonstrated by electrophoretic and immunologic techniques as the single protein constituent of amyloids isolated from Portuguese, Japanese and Swedish patients. The variant prealbumin of Japanese amyloid is characterised by methionine replacing valine as residue 30 and is identical to that found in plasma (but not as yet in amyloid) of affected Swedes. These limited data suggest that: (a) derivation of their amyloids from prealbumin is the biochemical common denominator of lower limb familial amyloidotic neuropathies regardless of the ethnic derivation of the afflicted; (b) to the extent that ethnic diversity reflects genetic heterogeneity, this will be demonstrable in the amyloid (and hopefully in the plasma) of the afflicted as entity-specific variant prealbumin monomers distinguished by different single amino acid substitutions; (c) on clinical and biochemical grounds, lower limb familial amyloidotic neuropathies include at least three genetic entities. In the upper limb and facial forms of familial amyloidotic polyneuropathy first recorded in Swiss and Finns respectively, the differences in their patterns of neurological disease and ocular lesions could be the result of their amyloids deriving from proteins other than prealbumin.