Clinical relevance of heterozygosis for aceruloplasminemia.
Marina Dorigatti BorgesDulcineia Martins de AlbuquerqueCarolina LanaroFernando Ferreira CostaKleber Yotsumoto FertrinPublished in: American journal of medical genetics. Part B, Neuropsychiatric genetics : the official publication of the International Society of Psychiatric Genetics (2019)
Aceruloplasminemia is a rare form of brain iron overload of autosomal recessive inheritance that results from mutations in the CP gene, encoding the iron oxidase ceruloplasmin. Homozygous aceruloplasminemia causes progressive neurodegenerative disease, anemia, and diabetes, and is usually diagnosed late in life upon investigation of anemia, high ferritin, or movement disorders, but its heterozygous state is less characterized and believed to be silent. Here we report two heterozygotes for new mutations causing aceruloplasminemia from whom peripheral blood samples were collected for complete blood counts, iron studies, and genotyping by automated sequencing. We then performed a systematic review of preview reports of heterozygotes with data on genotype and clinical findings. Heterozygosity for aceruloplasminemia invariably causes reduced ceruloplasmin levels, and similarly to previews reports in the literature, our cases did not present with anemia. Mild hyperferritinemia was found only in two reports. Nevertheless, 5 out of 11 variants have been associated with significant neurological symptoms despite the presence of one wild-type alelle. This review contributes to better genetic counseling of heterozygotes for CP gene variants and supports that measuring ceruloplasmin levels may be useful when investigating patients with movement disorders or rare cases of unexplained high ferritin.
Keyphrases
- iron deficiency
- copy number
- mitochondrial dna
- genome wide
- peripheral blood
- wild type
- adverse drug
- dna methylation
- high throughput
- type diabetes
- systematic review
- cardiovascular disease
- multiple sclerosis
- single cell
- white matter
- machine learning
- genome wide identification
- chronic kidney disease
- electronic health record
- big data
- intellectual disability
- early onset
- smoking cessation
- cerebral ischemia
- deep learning
- brain injury
- insulin resistance
- metabolic syndrome
- human immunodeficiency virus
- blood brain barrier
- antiretroviral therapy
- hepatitis c virus
- genome wide analysis