Infantile Systemic Hyalinosis: Novel Founder Mutation in the Initiation Codon among "Malis (Farmers)" in Jodhpur

Area of Science:

• Genetics
• Rare Diseases
• Molecular Biology

Background:

• Infantile systemic hyalinosis (ISH) is a rare, progressive autosomal recessive disorder.
• Characterized by hyaline material deposition in various tissues, leading to skin nodules, gingival hypertrophy, and joint contractures.
• ISH often results in severe complications and early mortality due to infections.

Purpose of the Study:

• To describe clinical features and genetic findings in five children with ISH from the Jodhpur mali community.
• To identify the underlying genetic cause of ISH in these families.
• To investigate the potential for a founder mutation within this community.

Main Methods:

• Clinical examination of five affected children from four unrelated families.
• Genetic analysis to identify mutations in the CMG2 (ANTXR2) gene.
• Segregation analysis of the identified mutation in family members.

Main Results:

• All five children presented with classical clinical features of ISH.
• Four children died from severe infections between 7 months and 3 years of age.
• A novel homozygous mutation (c.1 A>G; p. M1?) in the CMG2 gene was identified in two affected children.
• The same mutation was found in heterozygous form in two parents, suggesting a founder effect.

Conclusions:

• A novel mutation in the CMG2 gene is associated with infantile systemic hyalinosis.
• This mutation appears to be a founder mutation in the Jodhpur mali community.
• Early identification and genetic counseling are crucial for families with this disorder.