RESUMO
MOTIVATION: Next-generation sequencing (NGS) technologies are decisive for discovering disease-causing variants, although their cost limits their utility in a clinical setting. A cost-mitigating alternative is an extremely low coverage whole-genome sequencing (XLC-WGS). We investigated its use to identify causal variants within a multi-generational pedigree of individuals with retinitis pigmentosa (RP). Causing progressive vision loss, RP is a group of genetically heterogeneous eye disorders with approximately 60 known causal genes. RESULTS: We performed XLC-WGS in seventeen members of this pedigree, including three individuals with a confirmed diagnosis of RP. Sequencing data were processed using Illumina's DRAGEN pipeline and filtered using Illumina's genotype quality score metric (GQX). The resulting variants were analyzed using Expert Variant Interpreter (eVai) from enGenome as a prioritization tool. A nonsense known mutation (c.1625C > G; p.Ser542*) in exon 4 of the RP1 gene emerged as the most likely causal variant. We identified two homozygous carriers of this variant among the three sequenced RP cases and three heterozygous individuals with sufficient coverage of the RP1 locus. Our data show the utility of combining pedigree information with XLC-WGS as a cost-effective approach to identify disease-causing variants.
Assuntos
Proteínas do Olho , Retinose Pigmentar , Humanos , Códon sem Sentido , Análise Mutacional de DNA , Proteínas do Olho/genética , Proteínas Associadas aos Microtúbulos/genética , Mutação , Linhagem , Retinose Pigmentar/genética , Retinose Pigmentar/diagnóstico , Sequenciamento Completo do GenomaRESUMO
A 67-year-old woman with a history of hypertension and type 2 diabetes mellitus was admitted to the hospital due to aphasia and left-sided hemiparesis during the past 5 h with resolution of symptoms within 24 h. On admission laboratory analysis showed haemoglobin 19.2 g/dL and haematocrit 55.1%. Cerebral CT scan was also performed on admission revealing periventricular leucoaraiosis. Studies to investigate the cause of erythrocytosis were started and elevated erythropoietin levels were found. In order to investigate a secondary cause of erythrocytosis an abdominal ultrasound was conducted revealing a left renal mass. CT scans of thorax, abdomen and pelvis confirmed renal mass 8 × 8 cm of diameter, suggestive of neoplasm without associated lymphadenopathy or metastases. Radical nephrectomy was performed and a pathological diagnosis demonstrated clear cell renal cell carcinoma and was staged as T2aN0M0.
Assuntos
Carcinoma de Células Renais/complicações , Ataque Isquêmico Transitório/etiologia , Neoplasias Renais/complicações , Síndromes Paraneoplásicas/complicações , Policitemia/complicações , Idoso , Carcinoma de Células Renais/cirurgia , Diagnóstico Diferencial , Feminino , Humanos , Neoplasias Renais/cirurgia , Nefrectomia , Resultado do TratamentoRESUMO
Cutis verticis gyrata is a descriptive term for a condition of the scalp consisting of deep grooves and convolutions that resemble the surface of the brain. We present a case of a 22-year-old man who presented with pain and swelling of both knees and hands. Enlarged wrists, ankles and feet were also noted, along with facial seborrhoea, thickening of the skin and deformity of the fingers. Physical examination of the scalp showed a cerebriform appearance with accentuating folds and deep furrows (cutis verticis gyrata), thickening in the face, frontal and parietal regions. Bone enlargement of the hands, knees, ankles and feet was also found. Secondary causes of pachydermoperiostosis were negative.