Based on review of X-inactivation patterns in female carriers of other X-linked recessive diseases, our findings imply that substantial expression of a mutant ATP7A at the expense of the normal allele could be associated with neurologic symptoms in female carriers of Menkes disease and its allelic variants, occipital horn syndrome, and ATP7A-related distal motor neuropathy.
He has few neurological symptoms without connective tissue disturbances; and a missense ATP7A variant, p.(Pro852Leu), which results in impaired protein trafficking while the copper transport function is spared.
Since RS is mostly caused by mutations in the MECP2 gene, transgenic animal models such as the Mecp2-deleted ("Mecp2-null") mouse have been employed to study neurological symptoms and brain function.
We propose to implement DNA copy number testing for MECP2 in the current diagnostic testing in all males with moderate to severe mental retardation accompanied by (progressive) neurological symptoms.
Given the important function of MeCP2 in neuronal development, our data could shed light on how MeCP2 deficiency affects postnatal brain functions and the dynamic changes in the neurological symptoms of RTT.
Maintenance of an appropriate level of MeCP2 appears integral to the function of healthy neurons as patients with increased levels of MeCP2, owing to duplication of the Xq28 region encompassing the MECP2 locus, also present with intellectual disability and progressive neurologic symptoms.
This minimal protein is able to prevent or reverse neurological symptoms when introduced into MeCP2-deficient mice by genetic activation or virus-mediated delivery to the brain.
Interestingly, ACM from male, but not female MeCP2-Tg mice, displays this neurotoxicity reflecting the gender selectivity of neurological symptoms in mice.
Most of these findings were consistent with the newly established autosomal recessive disease "aceruloplasminaemia", except for the presence of serum Cp and the lack of apparent neurological symptoms.
Inherited functional deficiencies of ASA cause the lysosomal storage disease (LSD) metachromatic leukodystrophy (MLD), which is characterized by intralysosomal accumulation of sulfatide, progressive neurological symptoms and early death.
The presence of neurologic symptoms in patients with aceruloplasminemia is unique among the characterized disorders of iron metabolism, and recent findings indicate that astrocyte-specific ceruloplasmin gene expression is critical for iron metabolism and neuronal survival in the retina and basal ganglia.
Bone marrow stem cell gene therapy in mice, using a retroviral vector mediating expression of wild-type human ASA, has the potential to ameliorate the visceral pathology, but improves the prevailing brain disease and neurologic symptoms only marginally.
A 9-bp deletion (2320del9) on the background of the arylsulfatase A pseudodeficiency allele in a metachromatic leukodystrophy patient and in a patient with nonprogressive neurological symptoms.
Out of 8 cases with neurological symptoms and low ASA activity, 2 were found to be homozygous for the Pd allele; 2 MLD patients had healthy siblings homozygous for the Pd allele and another patient's allele bore two mutations, Pd and that causing MLD.
Analysis of the two PD mutations in the ASA gene separately was carried out in a large group of subjects with neurological symptoms and low ASA activity, including close relatives and MLD patients.
Hereditary hyperferritinemias are linked to mutations of three genes: the L-ferritin gene responsible for the hereditary hyperferritinemia cataract syndrome (without iron overload), the ferroportin gene leading to a dominant form of iron overload, and the ceruloplasmin (CP) gene corresponding to an iron overload syndrome with neurological symptoms.
The diagnosis of neurological disease is straightforward if the following symptoms are present: Kayser-Fleischer rings, typical neurological symptoms and low serum ceruloplasmin levels.
To overcome the diagnostic challenge, several clinical signs (Kayser-Fleischer rings, neurologic symptoms) and laboratory features (copper in serum, urine, liver; serum ceruloplasmin; genetic testing) are scored 0 (absent) to 2 (present) and the Leipzig score is calculated.
The diagnosis of Wilson's disease is based on clinical findings and laboratory abnormalities and can be made if two of the following symptoms are present: Kayser-Fleischer rings; topical neurologic symptoms; and low serum ceruloplasmin levels.
The presence of neurologic symptoms in aceruloplasminemia is unique among the known inherited and acquired disorders of iron metabolism; recent studies revealed an essential role for astrocyte-specific expression of ceruloplasmin in iron metabolism and neuronal survival in the central nervous system.