Biallelic Variant in HAPLN1 is Associated With Skeletal Dysplasia With or Without Congenital Heart Disease.
Reem M Elshafie, Hind Alsharhan, Hanai Abulabqah et al.
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Case in brief
Four individuals from an extended consanguineous Kuwaiti family had a skeletal dysplasia characterized by shortened long bones in the upper and lower limbs and short, stubby metacarpals. Imaging also showed square-shaped iliac wings, narrowed sciatic notches, flattened acetabular roofs, progressively narrowing lumbar interpedicular distance, and widened intervertebral disc spaces. Genetic analysis identified a homozygous missense variant in HAPLN1 that co-segregated with the phenotype. The authors propose HAPLN1 as a candidate gene for a newly described autosomal recessive skeletal dysplasia.
What made this case unusual
The report links a homozygous HAPLN1 variant to human skeletal dysplasia, extending the gene’s previously described association with skeletal dysplasia in mice to a human phenotype.
Diagnostic / clinical pearl
In a family with a compatible skeletal dysplasia phenotype, the combination of characteristic pelvic, spinal, and metacarpal findings may support genetic evaluation that includes HAPLN1.