Wisniewski K E, Zhong N, Kaczmarski W, Kaczmarski A, Sklower-Brooks S, Brown W T
Department of Pathological Neurobiology, New York State Institute for Basic Research in Developmental Disabilities, Staten Island 10314, USA.
Pediatr Neurol. 1998 Jan;18(1):36-40. doi: 10.1016/s0887-8994(97)00188-4.
In the United States, juvenile neuronal ceroid-lipofuscinosis (JNCL) is the most common form of NCL. This study analyzed 191 cases, diagnosed on the basis of age-at-onset, clinical symptomatology, and pathologic findings. Twenty percent (40/191) of these cases from 24/120 families manifested atypical clinical symptomatology and/or pathologic findings (typical revealed fingerprints and atypical revealed mixed inclusions, or only curvilinear or granular profiles) and, therefore, represent variant forms of JNCL. Those patients in the study with typical JNCL were a uniform group of cases, whereas the atypical were heterogenous and were divided into 8 subgroups based on the clinicopathologic findings. Forty-three families were analyzed (27 typical, 16 atypical) for the common 1.02 kb deletion and several pedigrees for novel mutations. In typical JNCL the common 1.02 kb deletion in both alleles (homozygous) were observed in 23/27, and only 1 allele (heterozygous) was exhibited in 4/27 families. In atypical JNCL families, 5/16 were heterozygous for the common 1.02 kb deletion. None of the remaining 11/16 families had the common 1.02 kb deletion in either allele, but in 9/11 cases the palmitoyl-protein thioesterase (PPT) levels were deficient. In cases where the mutation in CLN3 gene has not been identified, several possibilities may exist. The phenotype may be caused by a yet undefined mutation in CLN3 or may be due to overlapping with other forms of NCL.
在美国，青少年神经元蜡样脂褐质沉积症（JNCL）是神经元蜡样脂褐质沉积症（NCL）最常见的形式。本研究分析了191例病例，这些病例是根据发病年龄、临床症状和病理结果诊断出来的。来自120个家庭中的24个家庭的这些病例中有20%（40/191）表现出非典型的临床症状和/或病理结果（典型的表现为指纹状，非典型的表现为混合性包涵体，或仅为曲线状或颗粒状形态），因此，代表了JNCL的变异形式。该研究中具有典型JNCL的患者是一组统一的病例，而非典型患者则具有异质性，并根据临床病理结果分为8个亚组。对43个家庭（27个典型家庭，16个非典型家庭）进行了常见的1.02 kb缺失分析，并对几个家系进行了新突变分析。在典型的JNCL中，23/27的家庭观察到两个等位基因均存在常见的1.02 kb缺失（纯合子），4/27的家庭仅表现出1个等位基因（杂合子）。在非典型JNCL家庭中，5/16为常见的1.02 kb缺失杂合子。其余11/16的家庭中，没有一个家庭的任何一个等位基因存在常见的1.02 kb缺失，但在9/11的病例中，棕榈酰蛋白硫酯酶（PPT）水平不足。在未鉴定出CLN3基因突变的病例中，可能存在几种可能性。该表型可能是由CLN3中尚未明确的突变引起的，也可能是由于与其他形式的NCL重叠所致。
