Homozygous germline c.3380C>G missense mutation in PNPLA6 gene in a case of Gordon Holmes syndrome associated with hypogonadotropic hypogonadism, cerebellar ataxia, and juvenile type tremor

Gordon Holmes syndrome (GDHS) is a genetic disorder that is inherited in an autosomal recessive manner. It is characterized by the presence of cerebellar ataxia, which refers to a lack of coordination and control of voluntary movements, and hypogonadotropic hypogonadism, which is a condition where the production of hormones that regulate sexual development and function is reduced. In this report, we describe the case of a Turkish patient who has been diagnosed with GDHS. The cause of this syndrome in the patient is a homozygous new mutation in the PNPLA6 gene. The proband case was detected through a collaboration between neurology and medical genetics based on her clinical symptoms. The specific point mutation was identified using the next-generation sequencing (NGS) technology. The patient, who was 28 years old, presented with primary amenorrhea, tremors in her head and both hands, cognitive impairment, cerebellar ataxia, hypogonadotropic hypogonadism, and diabetes. A point mutation, specifically a germline missense mutation c.3380C>G, was identified in exon 31 of the PNPLA6 (NM006702.5) gene. This gene is responsible for encoding the neuropathy target esterase protein. The mutation was found by NGS screening. Her parents were consanguineous and both heterozygous for the same missense mutation. This instance highlights the significant impact of first-degree consanguineous marriage on our nation, particularly in relation to autosomal recessive hereditary illnesses. It underscores the crucial function of genetic counseling in averting such scenarios. Subsequent findings of PNPLA6 variants will provide more elucidation on the correlation between patient genotype and phenotype. The finding of novel variations in every gene has been made feasible by the recent progress of genomic technology.