✦ LIBER ✦

Mild-onset presentation of Canavan's disease associated with novel G212A point mutation in aspartoacylase gene

✍ Scribed by Christopher G. Janson; Edwin H. Kolodny; Bai-Jin Zeng; Srinivasa Raghavan; Gregory Pastores; Paola Torres; Mitra Assadi; Scott McPhee; Olga Goldfarb; Beth Saslow; Andrew Freese; D. J. Wang; Larissa Bilaniuk; David Shera; Paola Leone

Publisher: John Wiley and Sons
Year: 2006
Tongue: English
Weight: 63 KB
Volume: 59
Category: Article
ISSN: 0364-5134
DOI: 10.1002/ana.20787

No coin nor oath required. For personal study only.

✦ Synopsis

Abstract

We describe two sisters with a mild‐onset variant of Canavan's disease who presented at age 50 and 19 months with developmental delay but without macrocephaly, hypotonia, spasticity, or seizures. Remarkably, both patients had age‐appropriate head control, gross motor development, and muscle tone. There were very mild deficits in fine motor skills, coordination, and gait. Both sisters had a history of strabismus, but otherwise vision was normal. The older child showed evidence of mild cognitive and social impairment, whereas language and behavior were normal for age in the infant. Both patients were found to be compound heterozygotes for C914A (A305E) and G212A (R71H) mutations in ASPA. Like all other known ASPA mutations, this previously unknown G212A mutation appears to have low absolute enzyme activity. Nevertheless, it is associated in these patients with an extremely benign phenotype that is highly atypical of Canavan's disease. Biochemical and clinical data were evaluated using a generalized linear mixed model generated from 25 other subjects with Canavan's disease. There were statistically significant differences in brain chemistry and clinical evaluations, supporting a distinct variant of Canavan's disease. Future studies of ASPA enzyme structure and gene regulation in these subjects could lead to a better understanding of Canavan's pathophysiology and improvements in ASPA gene therapy Ann Neurol 2006;59:428–431

📜 SIMILAR VOLUMES

Identification of a novel point mutation

Identification of a novel point mutation (S65T) in α-galactosidase A gene in Chinese patients with Fabry disease

✍ Chia-Hsiang Chen; Pei-Wen Shyu; Su-Jen Wu; Song-Shan Sheu; Robert J. Desnick; Kw 📂 Article 📅 1998 🏛 John Wiley and Sons 🌐 English ⚖ 125 KB 👁 1 views

Fabry disease is an X-linked inborn error of sphingolipid catabolism resulting from deficient enzyme activity of a-galactosidase A. The molecular defects of human a-galactosidase A gene causing Fabry disease have been characterized, including gene rearrangement and point mutations, which show the ge

A novel missense point mutation (S134N)

A novel missense point mutation (S134N) of the Cu/Zn superoxide dismutase gene in a patient with familal motor neuron disease

✍ M Watanabe; M Aoki; K Abe; M Shoji; T Iizuka; Y Ikeda; S Hirai; K Kurokawa; T Ka 📂 Article 📅 1997 🏛 John Wiley and Sons 🌐 English ⚖ 120 KB 👁 2 views

## Communicated by Francesco Giannelli (NCV) were in the normal range, and there was no finding of nerve conduction block. His younger brother had also been affected by MND. He had developed muscle weakness of the right upper limb at age 52, followed by muscle weakness and atrophy of all limbs, an

A novel missense mutation (G209R) in exo

A novel missense mutation (G209R) in exon 8 of the presenilin 1 gene in a Japanese family with presenile familial Alzheimer's disease

✍ Naoya Sugiyama; Kyoko Suzuki; Takehiko Matsumura; Chiaki Kawanishi; Hideki Onish 📂 Article 📅 1999 🏛 John Wiley and Sons 🌐 English ⚖ 17 KB 👁 2 views

Over fifty missense mutations in the presenilin-1 (PSEN1) gene have been reported in families with presenile familial Alzheimer's disease (FAD). We describe a novel missense mutation (G209R) within the predicted fourth transmembrane domain of the PSEN1 in a Japanese family with presenile FAD. The af