Genetic analysis of a Chinese family affected with α-dystroglycanopathy due to variant of B3GALNT2 gene / 中华医学遗传学杂志

OBJECTIVE@#To explore the genetic basis for a Chinese pedigree affected with recurrent fetal hydrocephalus.@*METHODS@#A couple who had presented at the Affiliated Hospital of Putian College on March 3, 2021 was selected as the study subject. Following elective abortion, fetal tissue and peripheral blood samples were respectively obtained from the abortus and the couple, and were subjected to whole exome sequencing. Candidate variants were verified by Sanger sequencing.@*RESULTS@#The fetus was found to harbor compound heterozygous variants of the B3GALNT2 gene, namely c.261-2A>G and c.536T>C (p.Leu179Pro), which were inherited from its father and mother, respectively.According to the guidelines of American College of Medical Genetics and Genomics, both variants were classified as pathogenic (PVS1+PM2_Supporting; PM3+PM2_Supporting+PP3+PP4).@*CONCLUSION@#The compound heterozygous variants of the B3GALNT2 gene probably underlay the α-dystroglycanopathy in this fetus. Above results have provided a basis for genetic counseling of this pedigree.

Walker-Warburg syndrome features and gene study: a report of two cases

Walker-Warburg syndrome [WWS] is a rare autosomal recessive disorder characterized by congenital muscular dystrophy [CMD] and brain and eye abnormalities. Two other diseases have similar features, namely, muscl-eye-brain disease [MED] and Fukuyama congenital muscular dystrophy [FCMD]. The brain abnormalities in WWS are characterized by type 2 cobblestone lissencephaly, hydrocephalus, cerebellar malformations and brain stem anomalies. Mutations in protein O-mannosyltransferase 1 and 2 [POMT1 and POMT2] genes were found in 20% of WWS cases. Other rare mutations were found in Fukutin and Fukutin-related protein [FKRP] genes. We report cases of two Kuwaiti boys with WWS, who had typical brain magnetic resonance imaging [MRI] features. Both were screened for POMT1, POMT2, POMGnT1, FKRP and LARGE gene mutations and were negative. To the best of our knowledge these are the first two cases to be screened for known WWS gene mutations in Kuwait