Inheritance of Megaconial congenital muscular dystrophy (CMD)
Megaconial CMD is an autosomal recessive disorder so this genetic condition can be passed down from parent to child. The affected child must have two copies of an abnormal CHKB gene for the disease to develop, and usually inherits one copy of a mutated CHKB gene from each parent. The parents of the child with an autosomal recessive disorder usually do not have the disorder and is asymptomatic.
CHKB mutations and the clinical impact
CHKB gene is located on the long arm of chromosome 22 and contains 11 exons. Same biallelic pathogenic mutations (homozygous mutations) or different biallelic pathogenic mutations (compound heterozygous mutations) have been found in CHKB. Different types of CHKB mutations can occur in all the 11 exons across the gene.
The CHKB protein, also known as Choline kinase beta (CK), is a protein encoded by the CHKB gene. The CHKB protein is involved in the phospholipid synthesis. The phospholipids are essential membrane components of human cells. It is suggested that the disruption of the phospholipid de novo biosynthetic pathway play an important role in causing the Megaconial CMD with multi-system dysfunction affecting the muscle, brain and heart.
Diagnostic testing
Megaconial CMD can be diagnosed by suggestive clinical characteristics with genetic testing to detect biallelic CHKB gene mutations. The genetic testing can be by targeted single gene sequencing, muscular dystrophy multi-gene panel or whole exome sequencing.
CHKB