The Genetic Analysis Of A Congenital Nystagmus Pedigree And A Congenital Nephrotic Syndrome Pedigree

The first section:The genetic analysis of a congenital nystagmus pedigreeBackgrounds:Congenital nystagmus (CN) is a common oculomotor disorder. It is characterized by involuntary, rhythmical, repeated oscillations of one or both eyes with onset typically at birth or within the first few months of life. Patients'oscillations can be horizontal, vertical, torsional, although horizontal is the most common. CN is genetically heterogeneous. Two genes responsible for CN have been identified (i.e., the GPR143 gene for CN-6 and the FRMD7 gene for X-linked CN-1).Purpose:The purpose of the current research was to detect the underlying genetic defect in a Chinese family with X-linked congenital nystagmus and perform prenatal genetic diagnosis for their current pregnancy.Methods:A common clinical examination and an ophthalmic evaluation were performed on some of the family members. Mutation analysis of the GPR143 and FRMD7 genes was carried out by direct sequencing of PCR-amplified exons in the proband. The detected mutation was tested in all available family members and 50 normal controls by direct sequencing.Results:Congenital nystagmus, obvious fundus hypopigmentation, and foveal hypoplasia were observed in the proband. A novel splicing mutation c.658+1 g>t not found in 50 unrelated controls was identified and co-segregated with X-linked ocular albinism (XLOA) in this family. The fetus (V5) was hemizygous for this mutant allele. The FRMD7 gene's detection was normal. Conclusions:We identified a novel causative splicing mutation (c.658+1 g>t) of GPR143 in a five-generation Chinese family with XLOA.The second section:The genetic analysis of a congenital nephrotic syndrome pedigreeBackground:Homozygous mutations in the NPHS1 gene encoding nephrin account for～40% of infants with CNS. NPHS1 gene mutation can cause Finnish congenital nephrotic (CNF) which is a common CNS. The disease develops in utero and is diagnosed soon after birth, always presenting before 3 months of age on the basis of massive proteinuria. NPHS1 is enriched in the Finnish population with an incidence of 1:8200 newborns. There is a much lower frequency in other countries and there is no CNF statistical data for China. There is no effective treatment except renal transplantation to treat CNF, so it is necessary to do genetic diagnosis and prenatal diagnosis to prevent the birth of children.Purpose:The aim of this work was to investigate the disease-causing mutations in a Chinese family with CNF and to perform prenatal genetic diagnosis for their current pregnancy.Method:Mutation analysis of the NPHS1 and NPHS2 genes was carried out by direct sequencing of PCR-amplified exons in the couple. The detected mutation was tested in the fetus and 50 normal controls by direct sequencing. Results:A heterozygous nonsense mutation within exon 20 (c.2783C>A) and a missense mutation within exon 17 (c.2225T>C) in NPHS1 were detected in the proband's father and mother respectively, but not found in the fetus and 50 unrelated controls. The NPHS2 gene's detection was normal.Conclusion:Two novel mutations of C.2783C>A and c.2225T>C in NPHS1 were found to be causative in a Chinese CNF family with no known Finnish ancestry. The fetus did not inherit these two mutations and hence is unaffected with CNF.