A new large deletion at 1q24.3q25.3 locus in a patient with growth hormone deficiency and natural anticoagulants deficiency

Abstract

Introduction. Deletions at the 1q23q25 locus cause a distinctive phenotype including proportionate short stature, microcephaly, brachydactyly, dysmorphic facial features, and intellectual disability. Other less commonly reported features include renal, cardiac and genital malformations, craniosynostosis, and single palmar crease.
Objective. To identify and characterize a novel deletion at the 1q24.3q25.3 locus in a proband with growth hormone deficiency and natural anticoagulant deficiency.
Methods. The proband was a 7-year-old girl with proportionate intrauterine growth retardation, congenital heart defects, hyperfibrinogenemia and antithrombin III deficiency. The only case in the family. Differential diagnoses included microchromosomal pathology and acromelic dysplasia. Whole genome sequencing was performed for the mother and proband. The father is categorically against any research.
Results. The proband has a heterozygous deletion at the 1q24.3q25.3 locus, which is about 9.232 Mb. This deletion includes the following genes with an autosomal dominant type of inheritance: LHX4, SERPINC1, XPR1, MYOC, FASLG.
Conclusions. The study identified a deletion of the long arm of chromosome 1. This new mutation is the first identified case of a deletion syndrome at the 1q23q25 deletion locus in Russia and is the cause of short stature, facial dysmorphia, and thrombophilia in the proband. Early detection of this syndrome and proactive intervention may improve quality of life.