共查询到20条相似文献，搜索用时 15 毫秒
1.
Vykuntaraju K. Gowda Tamilarasan Udhayabanu Perumal Varalakshmi Varunvenkat M. Srinivasan Balasubramaniem Ashokkumar 《Brain & development》2018,40(7):582-586
Background
Fazio-Londe syndrome also called progressive bulbar palsy of childhood is a very rare motor neuron disease of pediatric age group characterized by progressive paralysis of lower cranial nerves.Objective
To describe Fazio-Londe syndrome in sibling with different phenotype.Methods
A 6?years old female child presented with inability to close eyes, difficulty in swallowing, respiratory muscle weakness and voice change since 5?yr of age. Examination showed lower motor neuron facial nerve palsy, absent gag reflex, tongue atrophy, fasciculation, limb wasting and exaggerated deep tendon reflexes. An 11?year old boy, elder sibling of the above child presented with similar complaints at 10?years of age, other than later onset and lack of respiratory problem. Genetic testing in both cases confirmed the diagnosis of Fazio-Londe Syndrome.Conclusion
In any child who presents with progressive bulbar palsy with lower motor neuron facial palsy a diagnosis of Fazio-Londe Syndrome should be considered and family members should also be screened. 相似文献2.
Masayuki Itoh Shuhei Ide Yuji Iwasaki Takashi Saito Keishi Narita Hongmei Dai Shinji Yamakura Takeki Furue Hirotsugu Kitayama Keiko Maeda Eihiko Takahashi Kiyoshi Matsui Yu-ichi Goto Sen Takeda Masataka Arima 《Brain & development》2018,40(4):259-267
Objective
Arima syndrome (AS) is a rare disease and its clinical features mimic those of Joubert syndrome or Joubert syndrome-related diseases (JSRD). Recently, we clarified the AS diagnostic criteria and its severe phenotype. However, genetic evidence of AS remains unknown. We explored causative genes of AS and compared the clinical and genetic features of AS with the other JSRD.Patients and methods
We performed genetic analyses of 4 AS patients of 3 families with combination of whole-exome sequencing and Sanger sequencing. Furthermore, we studied cell biology with the cultured fibroblasts of 3 AS patients.Results
All patients had a specific homozygous variant (c.6012-12T>A, p.Arg2004Serfs*7) or compound heterozygous variants (c.1711+1G>A; c.6012-12T>A, p.Gly570Aspfs*19;Arg2004Serfs*7) in centrosomal protein 290?kDa (CEP290) gene. These unique variants lead to abnormal splicing and premature termination. Morphological analysis of cultured fibroblasts from AS patients revealed a marked decrease of the CEP290-positive cell number with significantly longer cilium and naked and protruded ciliary axoneme without ciliary membrane into the cytoplasm.Conclusion
AS resulted in cilia dysfunction from centrosome disruption. The unique variant of CEP290 could be strongly linked to AS pathology. Here, we provided AS specific genetic evidence, which steers the structure and functions of centrosome that is responsible for normal ciliogenesis. This is the first report that has demonstrated the molecular basis of Arima syndrome. 相似文献3.
Toru Takaori Akira Kumakura Atsushi Ishii Shinichi Hirose Daisuke Hata 《Brain & development》2017,39(1):72-74
Background
SCN1A is the gene that codes for the neuronal voltage-gated sodium-channel alpha-subunit 1. It is generally considered that an SCN1A truncating mutation causes the severe phenotype of Dravet syndrome.Patients
We describe 11- and 4-year-old male patients presenting with mild Dravet syndrome with a truncating mutation of SCN1A. The former patient showed moderate mental retardation; however, seizure was controlled to almost one incident a year by levetiracetam and topiramate. Carbamazepine was also effective, which is atypical of Dravet syndrome. The latter patient showed a borderline developmental quotient and did not have episodes of afebrile seizure.Conclusion
Two patients presented with mild Dravet syndrome, even though they had a truncating mutation of SCN1A. Not all truncating mutations of SCN1A cause the severe phenotype of Dravet syndrome. 相似文献4.
Hyun Woo Kim Zhejiu Quan Young-Beom Kim Eunji Cheong Heung Dong Kim Minjung Cho Jiho Jang Young Rang Yoo Joon Soo Lee Ji Hun Kim Yang In Kim Dae-Sung Kim Hoon-Chul Kang 《Brain & development》2018,40(4):287-298
Background
We investigated how two distinct mutations in SCN1A differentially affect electrophysiological properties of the patient-derived GABAergic neurons and clinical severities in two Dravet syndrome (DS) patients.Materials and Methods
We established induced pluripotent stem cells from two DS patients with different mutations in SCN1A and subsequently differentiated them into forebrain GABAergic neurons. Functionality of differentiated GABAergic neurons was examined by electrophysiological recordings.Results
DS-1 patient had a missense mutation, c.4261G?>?T [GenBank: NM_006920.4] and DS-2 patient had a nonsense frameshift mutation, c.3576_3580 del TCAAA [GenBank: NM_006920.4]. Clinically, contrary to our expectations, DS-1 patient had more severe symptoms including frequency of seizure episodes and the extent of intellectual ability penetration than DS-2 patient. Electrophysiologic recordings showed significantly lower sodium current density and reduced action potential frequency at strong current injection (>60?pA) in GABAergic neurons derived from both. Intriguingly, unique genetic alterations of SCN1A differentially impacted electrophysiological impairment of the neurons, and the impairment’s extent corresponded with the symptomatic severity of the donor from which the iPSCs were derived.Conclusion
Our results suggest the possibility that patient-derived iPSCs may provide a reliable in vitro system that reflects clinical severities in individuals with DS. 相似文献5.
Daiki Kondo Atsuko Noguchi Ikuko Takahashi Hiroki Kubota Tamami Yano Yoko Sato Miyuki Toyono Yukio Sawaishi Tsutomu Takahashi 《Brain & development》2018,40(9):760-767
Objective
To reveal a molecular lesion in the ZC4H2 gene in a Japanese family with arthrogryposis multiplex congenita (AMC) and intellectual disability (ID), and to characterize clinical features of patients with ZC4H2 gene mutations through a literature review.Patients
The probands are male siblings. The elder brother is an 11-year-old boy who showed AMC and ID and frequent postprandial hypoglycemia since 3?years of age. The younger brother also showed AMC, ID, and subclinical postprandial hypoglycemia. The boys’ mother also showed a minor malformation of the left toes.Method and result
Using Sanger sequencing, a hemizygous one base substitution designated c.627G?>?C, which is predicted to substitute asparagine for lysine at amino acid residue 209 (K209N), was identified in the siblings. The mother was heterozygous for this mutation. In silico analysis predicted K209N to be a constituent of a motif required for subcellular localization of the ZC4H2 protein in the nucleus. Transient expression studies of subcellular localization in COS-7 cells showed that compared to the wild-type protein, the transport of the mutant protein into the nucleus was inhibited, thus confirming K209N as a molecular lesion in this family. The literature reviews revealed postprandial hypoglycemia as a new clinical feature that should be considered in ZC4H2 gene-mutation disorders.Conclusion
A Japanese family with AMC and ID caused by a novel ZC4H2 gene mutation was reported. Hypoglycemia should be considered one of the features in this disorder. 相似文献6.
Yusuke Takezawa Hiromi Fujie Atsuo Kikuchi Tetsuya Niihori Ryo Funayama Matsuyuki Shirota Keiko Nakayama Yoko Aoki Masayuki Sasaki Shigeo Kure 《Brain & development》2018,40(10):934-938
Background
IARS2 encodes isoleucine-tRNA synthetase, which is aclass-1 amino acyl-tRNA synthetase. IARS2 mutations are reported to cause Leigh syndrome or cataracts, growth hormone deficiency, sensory neuropathy, sensorineural hearing loss, and skeletal dysphasia syndrome (CAGSSS). To our knowledge, IARS2 mutations and diseases related to it have only been reported in three families. Here we report a case of two Japanese siblings with Leigh syndrome, some features of CAGSSS, and West syndrome that are found to have compound heterozygous novel IARS2 mutations.Case report
A 7-month-old Japanese girl presented with infantile spasms. Brain magnetic resonance imaging (MRI) revealed diffuse brain atrophy and hyperintensity in the bilateral basal ganglia. Three years later, her younger sister also presented with infantile spasms. MRI revealed diffuse brain atrophy and hyperintensity of the bilateral ganglia, suggesting Leigh syndrome. The siblings were identified with compound heterozygous missense mutations in IARS2, p.[(Phe227Ser)];[(Arg817His)].Conclusion
This is the first case study reporting Leigh syndrome concomitant with some features of CAGSSS in siblings with novel IARS2 mutations, thereby broadening the phenotypic spectrum of IARS2-related disorders. Further studies are warranted to elucidate the nature of these disorders. 相似文献7.
Yohane Miyata Ken Saida Satoko Kumada Noriko Miyake Hideaki Mashimo Yuya Nishida Ikuko Shirai Eiji Kurihara Yasuhiro Nakata Naomichi Matsumoto 《Brain & development》2018,40(7):566-569
Background
Coffin-Lowry syndrome is a rare X-linked disease, caused by loss-of-function mutations in the RPS6KA3 gene. Patients exhibit severe intellectual disability with characteristic dysmorphism. As there are no specific laboratory findings to support the diagnosis of Coffin-Lowry syndrome, it may be difficult to diagnose—especially in young children, where the characteristic craniofacial features are less discernible.Case
Here we report on a 2-year-old boy with Coffin-Lowry syndrome with a novel missense mutation in the RPS6KA3 gene. On magnetic resonance imaging, his brain exhibited periventricular signal abnormalities with multiple small cystic lesions. These findings may aid in diagnosis of Coffin-Lowry syndrome. 相似文献8.
Masashi Ogasawara Akihiko Ishiyama Akira Sugiura Kazuhiko Segawa Ikuya Nonaka Eri Takeshita Yuko Shimizu-Motohashi Hirofumi Komaki Masayuki Sasaki 《Brain & development》2018,40(4):339-342
Introduction
Chilaiditi syndrome is a rare pathophysiology in which the colon or other organs are interposed between the diaphragm and liver, and respiratory or digestive symptoms sometimes manifest. Although there have been some cases of Chilaiditi syndrome complicating neuromuscular disorders, none have described resulting respiratory or digestive symptoms.Case presentation
Our patient was a 20-year-old man with DMD who had been receiving noninvasive positive-pressure ventilation during the night. He experienced respiratory distress when changing from a supine to sitting position. Ventilator adjustment did not relieve the respiratory distress. Abdominal computed tomography revealed marked constipation and interposition of the transverse colon between the diaphragm and liver, indicating Chilaiditi syndrome. The right side of the diaphragm was elevated by the interposed transverse colon when the respiratory distress was present on chest radiograph, but not when symptoms were absent. The patient was diagnosed with platypnea-orthodeoxia attributed to Chilaiditi syndrome. The respiratory distress was improved by the relief of constipation, in addition to the usage of the ventilator throughout the day.Conclusion
The rare symptoms and pathophysiology of DMD complicated by Chilaiditi syndrome are reported and discussed herein. 相似文献9.
Takeshi Kouga Mariko Takagi Akihiko Miyauchi Hiroko Shimbo Mizue Iai Sumimasa Yamashita Kei Murayama Matthew B. Klein Guy Miller Tomohide Goto Hitoshi Osaka 《Brain & development》2018,40(2):145-149
Background
Leigh syndrome is a mitochondrial disease caused by respiratory chain deficiency, and there are no proven effective therapies. EPI-743 is a potent cellular oxidative stress protectant and results of clinical trials for mitochondrial diseases are accumulating.Case
At 5 months, a girl presented with the scarce eye movement and diminished muscle tone. She was diagnosed with Leigh encephalopathy from blood and cerebrospinal fluid lactate elevation and MRI findings. Sequence analysis for mitochondrial DNA revealed a T10158C mutation in the mitochondrial encoded ND3 gene in complex I.Results
At 8 months, succinate was prescribed expected to restore the electron transport chain system. After that her condition got worse and succinate was discontinued. Subsequent administration of EPI-743 improved her eye movement, fine motor movements of the extremities, and bowel movement. She is now 5 years old. Although brain atrophy has progressed, she has still respiratory free time.Conclusion
Our patient showed visible improvement with EPI-743 treatment and the only patient surviving after 4 years. There is a possibility that EPI-743 is modifying the natural course of the syndrome. 相似文献10.
Karin Kojima Kentaro Shirai Mizuki Kobayashi Akihiko Miyauchi Hirotomo Saitsu Naomichi Matsumoto Hitoshi Osaka Takanori Yamagata 《Brain & development》2018,40(1):69-73
Background
The potassium voltage-gated channel subfamily Q member 2 (KCNQ2) gene has been reported to be associated with various types of epilepsy, including benign familial neonatal seizure (BFNS), early infantile epileptic encephalopathy (EIEE), and unclassified early onset encephalopathies. We herein report a patient with early myoclonic encephalopathy (EME) caused by a KCNQ2 mutation.Case report
A male infant started to exhibit erratic myoclonus several days after birth and apnea attacks lasting for seconds with desaturation. One month after birth, his myoclonuses worsened in frequency. Electroencephalogram (EEG) showed a burst and suppression pattern, and myoclonuses occurred in the burst phase with diffuse polyspikes on EEG. At five months, inter-ictal EEG revealed hypsarrhythmia, but his attacks were still only myoclonuses. ACTH treatment was effective and the myoclonus frequency markedly decreased. At one year of age, whole-exome sequencing revealed a heterozygous mutation of the KCNQ2 gene (NM_172107.2): c.601C > T; p.(Arg201Cys), which was confirmed as de novo by Sanger sequencing. This mutation lies within the extracellular portion of the S4 voltage sensor.Conclusion
Most patients with a KCNQ2 mutation present with seizures starting in the neonatal period with varying severity, ranging from BFNS to Ohtahara syndrome. Furthermore, KCNQ2 appears to be a causative gene for EME. 相似文献11.
Hiroo Tani Nobutsune Ishikawa Yoshiyuki Kobayashi Shohei Yamaoka Yuji Fujii Kimihiko Kaneko Toshiyuki Takahashi Masao Kobayashi 《Brain & development》2018,40(10):943-946
Background
Rett syndrome (RTT) is a neurodevelopmental disorder primarily caused by mutations in the methyl-CpG-binding protein 2 (MECP2) gene, resulting in developmental regression after normal development during infancy. Transient presentation of many autistic features is also commonly seen in RTT. Anti-myelin oligodendrocyte glycoprotein (MOG)-antibody encephalitis is an acquired relapsing demyelinating syndrome characterized by a variety of neuroinflammatory symptoms. Here, we report a case of anti-MOG antibody encephalitis in a patient with genetically confirmed RTT, which mimicked many of the features of RTT.Case report
A three-year-old girl presented with subacute verbal and motor dysfunction, along with involuntary movements and marked irritability. Magnetic resonance imaging (MRI) revealed extensive white matter lesions, with anti-MOG antibodies detected in the serum and cerebrospinal fluid, resulting in an initial diagnosis of anti-MOG antibody encephalitis. However, additional testing of the MECP2 gene was performed in response to persistent involuntary hand movements in combination with progressive verbal and motor deterioration. Sequencing analysis revealed a known pathogenic mutation in MEPC2, indicating a concurrent diagnosis of RTT.Conclusion
Both RTT and anti-MOG antibody encephalitis are rare conditions. Similarities in disease presentation suggest that anti-MOG antibody encephalitis may mimic many of the symptoms of RTT. 相似文献12.
Chizuko Nakamura Yuji Inaba Keiko Tsukahara Mie Mochizuki Emi Sawanobori Yozo Nakazawa Kouki Aoyama 《Brain & development》2018,40(2):159-162
Background
Cat scratch disease is a common infectious disorder caused by Bartonella henselae that is transmitted primarily by kittens. It typically exhibits a benign and self-limiting course of subacute regional lymphadenopathy and fever lasting two to eight weeks. The most severe complication of cat scratch disease is involvement of the nervous system, such as encephalitis, meningitis, and polyneuritis. Peripheral facial nerve palsy associated with Bartonella infection is rare; few reported pediatric and adult cases exist and the precise pathogenesis is unknown.Case report
A previously healthy 7-year-old boy presented with fever, cervical lymphadenopathy, and peripheral facial nerve palsy associated with serologically confirmed cat scratch disease. The stapedius muscle reflex was absent on the left side and brain magnetic resonance imaging revealed a mass lesion at the left internal auditory meatus. The patient’s symptoms and imaging findings were gradually resolved after the antibiotics and corticosteroids treatment.Conclusions
The suspected granulomatous lesion was considered to have resulted from the host’s immune reaction to Bartonella infection and impaired the facial nerve. This is the first case report providing direct evidence of peripheral facial nerve palsy caused by a suspected granulomatous lesion associated with cat scratch disease and its treatment course. 相似文献13.
Background
Hemiconvulsion-hemiplegia-epilepsy (HHE) involves infantile-onset acute hemiconvulsive febrile status epilepticus with subsequent unilateral cerebral atrophy and hemiparesis. Chronic epilepsy later develops, typically involving refractory focal seizures; however, the underlying pathophysiology of this epilepsy is not well understood.Patient
We present a boy who had a typical acute presentation of HHE at 23?months, but an unusual evolution to chronic epilepsy in which the initially unaffected hemisphere was significantly abnormal. His initial acute presentation was right-sided hemiconvulsive febrile status epilepticus, with subsequent left cerebral hemiatrophy and hemiparesis affecting the right face, arm and leg. Focal seizures began at 5?years and were refractory to medical treatment. At 9?years, video EEG monitoring showed a striking pattern of interictal slow spike-wave and paroxysmal fast activity, maximal over the right, initially unaffected, hemisphere. He had primarily focal tonic seizures involving left-sided stiffening, also appearing to originate from the right hemisphere. Following left functional hemispherotomy he became seizure-free and parents reported improved cognitive function, attention and quality of life.Discussion
This boy had classic features of Lennox-Gastaut syndrome, but expressed almost exclusively over the right hemisphere, which was initially unaffected in his acute presentation of HHE. His evolution to “hemi-Lennox-Gastaut-like phenotype” illustrates the importance of monitoring chronic epilepsy in patients with HHE; early surgical intervention might prevent pathologic recruitment of bilateral secondary networks leading to the refractory seizures and cognitive impairment associated with Lennox-Gastaut syndrome. 相似文献14.
Lulu Kang Yu Wang Xiaolan Gao Wenjuan Qiu Jun Ye Lianshu Han Xuefan Gu Huiwen Zhang 《Brain & development》2018,40(10):876-883
Background
Gaucher disease (GD) is one of the most common lysosomal storage diseases resulting from a deficiency of glucocerebrosidase. Three main types have been described, with type 2 being the most rare and severe form. Here we investigated the clinical symptoms and mutation spectrum in 20 unrelated type 2 GD patients.Method
The diagnosis of GD was based on the acid β-glucocerebrosidase (GBA) enzyme activity and direct sequencing of the GBA gene. GBA activity was measured in leukocytes and the GBA gene was amplified by a polymerase chain reaction (PCR). For patient 7, the GBA gene was analyzed by PCR as well as quantitative real-time PCR.Results
The age of onset was under 12?months for all patients. All patients experienced severe neurological involvement. A total of 19 different GBA gene mutations were identified, including 6 novel mutations: two were exonic point mutations, c.1127T?>?C (p.Phe376Ser), c.1418T?>?G (p.Val473Gly); one was splicing error, ISV7-1G?>?C; one was insertion, c.717_718insACAG; and the other two were a gross deletion that involved exon 6 and a recombinant allele. The most prevalent mutation was Leu483Pro, which constituted 42.5% of all mutant alleles and was associated with a neurological form in Chinese GD patients as calculated by a Fisher’s exact test.Conclusion
The clinical characteristics of Chinese type 2 GD were consistent with reports from other ethnic populations. We identified 6 novel mutations that contribute to the spectrum of GBA gene mutations. Our study confirmed that GD patients with the Leu483Pro allele were prone to experience neurological symptoms. 相似文献15.
Background
Periodic paralysis (PP) is an autosomal dominant muscle disorder characterized by periodic muscle weakness attacks associated with serum potassium level variations. It is classified into hypokalemic (hypoKPP), hyperkalemic (hyperKPP), and normokalemic (normoKPP) forms based on the ictal serum potassium level. HyperKPP and normoKPP are caused by mutations of the same gene SCN4A, the gene encoding the skeletal muscle voltage-gated sodium channel. Prophylactic treatment with thiazide diuretics is highly effective in preventing attacks in hyperKPP. However, the efficacy and safety of such diuretics in normoKPP remain unclear.Case
We describe a familial case of normoKPP wherein the affected individuals showed periodic muscle weakness attacks, with an early childhood onset, and a lack of serum potassium level variation during the paralytic attacks. Sequencing analysis of SCN4A gene revealed a heterozygous missense mutation (c. 2111C?>?T, p. Thr704Met) in all symptomatic family members. Oral administration of hydrochlorothiazide, a thiazide diuretic, markedly improved the paralytic attack frequency and duration in the affected individuals without adverse effects.Conclusion
Our case demonstrates the efficacy of hydrochlorothiazide in the prophylactic treatment of normoKPP caused by the SCN4A mutation of p.Thr704Met, the most frequent mutation of hyperKPP. 相似文献16.
Purpose
The treatment options for Lennox–Gastaut syndrome (LGS), a pediatric epileptic syndrome, are limited, especially in younger children. Rufinamide tablets were safe and effective as an add-on treatment in Korean children and adolescents <20?years of age with LGS. This subgroup analysis aimed to evaluate the efficacy and safety of rufinamide tablets in LGS pediatric patients aged 1–4?years.Methods
This was a retrospective, observational study in LGS patients aged 1–4?years who received 12?weeks of treatment with rufinamide orally as an adjuvant treatment between April and June 2010. The proportion of responders (patients with a ≥50% reduction in seizure frequency after rufinamide treatment) was evaluated according to the type of seizure. The proportion of patients who were seizure-free was also evaluated. Adverse events (AEs) were evaluated after 12?weeks of treatment.Results
Among the 15 patients evaluated, one discontinued treatment because of worsening seizures 4?weeks after administration of rufinamide. Seven (46.67%) patients were responders and four patients were seizure-free. There were four responders with convulsive seizures, one each for myoclonic seizures and drop attacks, and spasms. The responder rate was increased to 69.23% by long-term treatment of rufinamide. AEs were experienced by three patients. One patient each experienced somnolence, fatigue, and rash.Conclusion
Rufinamide tablets were efficacious and well tolerated in LGS patients aged 1–4?years, at doses up to 1000?mg per day, when given as add-on therapy to other antiepileptic drugs. 相似文献17.
Yukari Miyakawa Tatsuo Fuchigami Masako Aoki Yusuke Mine Junichi Suzuki Tatsuhiko Urakami Shori Takahashi 《Brain & development》2018,40(7):592-595
Background
Neurological manifestations caused by hypoglycemia range from reversible focal deficits and transient encephalopathy to irreversible coma or death. Recently, high signal intensity lesions in the splenium of the corpus callosum on diffusion-weighted magnetic resonance imaging were reported in adults experiencing hypoglycemia. However, patients presenting with agraphia are rare.Subject and methods
We examined a 17-year-old left-handed female patient with type 1 diabetes who exhibited transient left agraphia with a reversible splenium lesion of the corpus callosum on diffusion-weighted imaging caused by hypoglycemia, which was improved with blood glucose management alone.Conclusion
This rare case indicates that agraphia, a sign of callosal disconnection syndrome, can result from a reversible splenial lesion of the corpus callosum caused by hypoglycemia. 相似文献18.
Mieko Yoshioka Naoya Morisada Daisaku Toyoshima Hajime Yoshimura Hisahide Nishio Kazumoto Iijima Yasuhiro Takeshima Tomoko Uehara Kenjiro Kosaki 《Brain & development》2018,40(4):343-347
Introduction
The most common form of spinal muscular atrophy (SMA) is a recessive disorder caused by SMN1 mutations in 5q13, whereas the genetic etiologies of non-5q SMA are very heterogenous and largely remain to be elucidated. We present a father and son with atrophy and weakness of the lower leg muscles since infancy. Genetic studies in this family revealed a novel BICD2 mutation causing autosomal dominant lower extremity-predominant SMA type 2.Patients
The proband was the father, aged 30, and the son was aged 3. Both of them were born uneventfully to nonconsanguineous parents. While the father first walked at the age of 19?months, the son was unable to walk at age 3?years. In both, knee and ankle reflexes were absent and sensation was intact. Serum creatine kinase levels were normal. The son showed congenital arthrogryposis and underwent orthopedic corrections for talipes calcaneovalgus. Investigation of the father at the age of 5?years revealed normal results on nerve conduction studies and sural nerve biopsy. Electromyography showed chronic neurogenic change, and muscle biopsy showed features suggestive of denervation. The father was diagnosed clinically with a sporadic distal SMA. Follow-up studies showed very slow progression.Investigations and results
Next-generation and Sanger sequencing revealed a deleterious mutation in BICD2: c.1667A>G, p.Tyr556Cys, in this family.Discussion
BICD2 is a cytoplasmic conserved motor-adaptor protein involved in anterograde and retrograde transport along the microtubules. Next-generation sequencing will further clarify the genetic basis of non-5q SMA. 相似文献19.
Hyuna Kim Sangmoon Lee Murim Choi Hunmin Kim Hee Hwang JiEun Choi Jong Hee Chae Ki Joong Kim Byung Chan Lim 《Brain & development》2018,40(5):429-432
Purpose
A recurrent de novo mutation in KCNC1 (c.959G?>?A, p.Arg320His) has been identified recently as one of the important genetic causes of progress myoclonic epilepsy (PME). The clinical phenotype resulting from this mutation has been named as myoclonus epilepsy and ataxia due to potassium channel mutation (MEAK). This finding carries important clinical implications in that autosomal dominant inheritance and de novo occurrence need to be considered when conducting genetic tests in patients with PME. We present two familial cases of MEAK in siblings with a recurrent p.Arg320His mutation in KCNC1.Method
Whole exome sequencing and subsequent Sanger sequencing were performed for the cases and their parents.Results
A recurrent p.Arg320His mutation in KCNC1 was identified in the two brothers who showed characteristic features of MEAK: near normal early development, onset of myoclonus around 10?years of age, infrequent generalized tonic-clonic seizures, relatively mild cognitive impairment, and generalized epileptiform discharges. Interestingly, the asymptomatic mother was suspected as being mosaic for this mutation. This finding could lead to misleading inheritance patterns and make genetic diagnosis of PME more complicated.Conclusions
Our familial MEAK cases show that consideration of parental mosaicism in addition to meticulous phenotyping is needed when conducting KCNC1 genetic testing. 相似文献20.
Marco Luigetti Guido Primiano Cristina Cuccagna Daniela Bernardo Donato Sauchelli Catello Vollono Serenella Servidei 《Clinical neurophysiology》2018,129(8):1618-1623