Objective: To report a patient who presented with hypogonadotropic hypogonadism, chorioretinal dystrophy, and cerebellar ataxia. He has 2 missense variant mutations of PNPLA6.

Background: Boucher-Neuhäuser syndrome (BNS) (MIM215470) is characterized by three clinical features such as ataxia, hypogonadotropic hypogonadism, and chorioretinal dystrophy. BNS is inherited in an autosomal recessive pattern, and most cases of BNS are caused by patatin like phospholipase domain containing 6 (PNPLA6) gene mutations.

Method: patient
An 18-year-old male patient visited the movement subdivision, neurological department in our hospital because of a progressive gait disturbance that began two years ago. He had been diagnosed as retinitis pigmentosa at the age of 12 years. In the physical examination, he had no axillary and pubic hair and showed a small penis and testis. Neurological examination revealed mild dysarthria, vertical and horizontal gaze-evoked nystagmus, and ataxic gait. Endocrinological assessments including the luteinizing hormone (LH) and follicle‑stimulating hormone (FSH) were examined. He performed both chromosomal and genetic studies. He also was tested brain magnetic resonance imaging (b-MRI).
Whole exome sequencing
Genomic DNA was extracted from peripheral blood leukocytes (1 ml per patient). All exon regions of all human genes (~22,000) were captured by Agilent’s SureSelect kit. The captured regions of the genome were sequenced with an Illumina sequencing machine.

Results: The neurological examination revealed gaze-evoked nystagmus, dysmetria, and dysdiadochokinesia in upper limbs. Although serum prolactin, TSH, TH were within normal range, FSH and LH levels were low each 1.68 (3.4-33.4) and 1.02 (8.7-76.3). 
Ophthalmoscopic examination showed extensive atrophy of the retinal pigment epithelium and choriocapillaris in the posterior pole and mid periphery of both eyes, with some clumps of pigment deposition. B-MRI showed diffuse cerebellar atrophy and normal pituitary gland (Fig. 2). 
Two PNPLA6 mutations (c.3373G>A, p.Asp1125Asn and c.2912C>G, p.Ala971Gly) were identified.

Conclusion: BNS is usually diagnosed by clinical and neuroimaging results combined with biallelic pathogenic variants in PNPLA6. Our patient showed classical phenotype hallmarks such as hypogonadotropic hypogonadism, chorioretinal degeneration, and cerebellar ataxia. Genetic analysis was recently performed and showed 2 new variants of the PNPLA6 gene.

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MDS Abstracts - https://www.mdsabstracts.org/abstract/a-korean-first-case-of-boucher-neuhauser-syndrome-with-two-novel-mutations-of-pnpla6-gene/