Molecular Basis And Genetic Counseling

PWS is the result of deficiency of one or more genes that map on the proximal long arm of chromosome 15 (Table 2). These genes are imprinted. Only their paternally derived alleles are functional.1-3-1 The genomic imprinting on chromosome 15 is reflected in the patterns of cytosine methylation in the CpG islands of this region. These cytosines are methylated only in the maternally derived sequences in the imprinted area. These detectable differences can be used for the diagnostic workup of individuals with suspected PWS. Four mechanisms

Table 1 Consensus clinical diagnostic criteria for PWS

Type II

Major criteria (one point each)

Neonatal/infantile central hypotonia Feeding problems, failure to thrive Rapid weight gain between 1 and 6 years Characteristic facial features Hypogonadism

Developmental delay/mental retardation

Minor criteria (1/2 point each) Decreased fetal movements Abnormal behavior Sleep disturbances/sleep apnea Short stature Hypopigmentation Small hands/feet

Narrow hands with straight ulnar border Esotropia, myopia Thick viscous saliva Speech articulation defects Skin picking

Supportive findings High pain threshold Decreased vomiting Temperature instability Scoliosis/kyphosis Early adrenarche Osteoporosis

Unusual skill with jigsaw puzzles Normal neuromuscular studies

The diagnosis of PWS is strongly suspected in children under 3 years of age with five points (three from major criteria) and above 3 years of age with eight points (four from major criteria). Source: Adopted from Refs. [4] and [15].

can lead to PWS. (All but Type lib among those listed below have DNA methylation abnormalities and can be diagnosed using DNA methylation analysis; see Diagnostic Methods.)

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Getting Started With Dumbbells

Getting Started With Dumbbells

The use of dumbbells gives you a much more comprehensive strengthening effect because the workout engages your stabilizer muscles, in addition to the muscle you may be pin-pointing. Without all of the belts and artificial stabilizers of a machine, you also engage your core muscles, which are your body's natural stabilizers.

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