Genetics Neuro:

Red ragged muscle fibers are seen in mitochondrial diseases. Muscle fibers have this appearance because
abnormal mitochondria accumulate under the sarcolemma. Mitochondrial diseases show maternal
inheritance.
An increased number of trinucleotide repeats on the HD gene is associated with Huntington disease. The
larger the number of the repeats, the earlier the onset of the disease. Trinucleotide expansion occurs during
paternal transmission, causing a genetic phenomenon called anticipation.
Neurofibromatosis type l is a single-gene autosomal-dominant disorder. It occurs due to mutation of the
NF-1 gene located on the chromosome i 7. Cafe-au-lait spots, multiple neurofibromas, and Lisch nodules
are the most common symptoms.

Early-onset (<60y/o) familial Alzheimer disease is associated with three gene mutations: APP
(chromosome 21), presenilin 1 gene on chromosome 14 and presenilin 2 gene on chromosome 1. Lateonset familial Alzheimer disease is associated with apolipoprotein F4 genotype.
The familial mental retardation gene 1 (FMR1) is located on the long arm of the X chromosome. An
increased number of CGG trinucleotide repeats leads to hyper methetoin of cysteine bases and gene
inactivation. This defect is the cause of fragile X syndrome, which manifests with mental retardation1
facial dysmorphism, and macroorchidism.
Mitochondrial diseases are characterized by exclusively-maternal inheritance. The variable severity of
these diseases is explained by the random distribution of normal and mutated mitochondria between
daughter cells during mitosis; as a result, some cells may have completely healthy mitochondria, while
other cells contain mitochondria affected by genetic mutation (Heteroplasmy). MELAS is a mitochondrial
syndrome.

Alteration of gene expression in Huntington disease is believed to occur due to hyper methylation of
histones. Hypermethylated histones bind DNA and prevent transcription of certain genes. This leads to the
disruption of synthesis of some neutrophic proteins.
Friedreich ataxia is an autosomal recessive condition. The mutated gene on chromosome 9 has an increased
number of trinucleotide repeats. Friedreich ataxia is often associated with hypertrophic cardiomyopathy,
diabetes mellitus, kyphoscoliosis, and foot deformities.
Fragile X syndrome is a common cause of inherited mental retardation. The disorder is X-linked and affects
males. Patients have mental retardation, dysmorphic facial features (large jaw large protruding ears) and
macroorchidism.
Fragile X syndrome arises secondary to an increase in the number of trinucleotide repeats within the FMR1
gene on the X chromosome. Typical clinical features of this condition include mental retardation1 facial
deformities, and macroorchidism.

A -amyloid plays an important role in the development of Alzheimer disease. Its precursor protein (APP)
is coded by a gene located on chromosome 21. Patients with trisomy 21 (Down syndrome) are likely to
develop Alzheimer disease after age 40.
Other conditions associated with Down syndrome include:
1. Acute leukemias: both AML and ALL
2. Congenital heart disease: endocardial cusion defect, VSD, ASD
3. GIT defects: duodenal atresia and Hirschsprung disease