Gordon Holmes syndrome due to compound heterozygosity of two new PNPLA6 variants – A diagnostic challenge
| Autor: | Isabel Alonso, Paula Jorge, Paula Salgado, Rui Carvalho, Marina Magalhães, Daniel Dias, Ana Filipa Brandão, Cristina Ramos |
|---|---|
| Přispěvatelé: | Instituto de Investigação e Inovação em Saúde |
| Rok vydání: | 2019 |
| Předmět: |
Proband
congenital hereditary and neonatal diseases and abnormalities Pediatrics medicine.medical_specialty Ataxia PNPLA6 gene Case Report Compound heterozygosity Hypogonadotropic hypogonadism lcsh:RC346-429 03 medical and health sciences FMR1 gene 0302 clinical medicine medicine 030212 general & internal medicine Allele Index case lcsh:Neurology. Diseases of the nervous system Cerebellar ataxia business.industry medicine.disease FMR1 Gordon Holmes syndrome Neurology medicine.symptom business hormones hormone substitutes and hormone antagonists 030217 neurology & neurosurgery |
| Zdroj: | eNeurologicalSci, Vol 14, Iss, Pp 9-12 (2019) eNeurologicalSci |
| ISSN: | 2405-6502 |
| DOI: | 10.1016/j.ensci.2018.11.022 |
| Popis: | Background: Gordon Holmes syndrome (GHS), characterized by cerebellar ataxia and hypogonadotropic hypogonadism (HH), has been related to recessive mutations in PNPLA6 gene. Aims of the study: Describe one Portuguese family with GHS due to compound heterozygosity of two new PNPLA6 variants. Methods: Report on the clinical presentation, diagnostic and genetic workup to reach GHS diagnosis. Results: The index case presented with slight cognitive impairment and primary amenorrhea, developed at the age of 25 a cerebellar syndrome. Her neurological exam revealed ataxia and mild extrapyramidal syndrome. She was born from non-consanguineous parents and had 8 siblings. Two of her sisters also had history of primary amenorrhea, tremor and ataxia. All 3 were diagnosed with HH and previous FMR1 gene screening on her sisters revealed a 51 CGGs allele. However, 2 normal-sized FMR1 alleles were identified on the proband thus excluding the FXTAS diagnosis in the family. Further PNPLA6 variant screening revealed 2 novel variants in compound heterozygosity [c.2404G > C]; [c.4081C > T], which co-segregated with the disease. Conclusions: This case shows how incomplete studies can be misleading, increases genetic knowledge of GHS and expands its clinical spectrum. The coexistence of a FMR1 intermediate allele in this family constituted an additional challenge in the etiological investigation. Unit for Multidisciplinary Research in Biomedicine – UMIB/ICBAS/UP is supported by National Funds through the FCT – Fundação para a Ciência e Tecnologia (Portuguese national funding agency for science, research and technology) in the frameworks of the UID/Multi/0215/2016 project. |
| Databáze: | OpenAIRE |
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