Two cases of variant late infantile ceroid lipofuscinosis in Jordan

Nafi, Omar; Ramadan, Bashar; Rieß, Olaf; Buchert, Rebecca; Froukh, Tawfiq

doi:10.12998/wjcc.v7.i2.203

Cited by 8 publications

(9 citation statements)

References 23 publications

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“…As an example, in Jordan only a limited number of families with children with NDDs underwent extensive molecular testing in a research context leaving the majority of patients without a firm diagnosis. [5][6][7][8][9][10][11][12][13] This study aims to establish whole exome sequencing (WES) as first-tier diagnostics in undiagnosed neurodevelopmental cases in Jordan.…”

Section: Introductionmentioning

confidence: 99%

Genetic basis of neurodevelopmental disorders in 103 Jordanian families

et al. 2020

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We recruited 103 families from Jordan with neurodevelopmental disorders (NDD) and patterns of inheritance mostly suggestive of autosomal recessive inheritance. In each family, we investigated at least one affected individual using exome sequencing and an in‐house diagnostic variant interpretation pipeline including a search for copy number variation. This approach led us to identify the likely molecular defect in established disease genes in 37 families. We could identify 25 pathogenic nonsense and 11 missense variants as well as 3 pathogenic copy number variants and 1 repeat expansion. Notably, 11 of the disease‐causal variants occurred de novo. In addition, we prioritized a homozygous frameshift variant in PUS3 in two sisters with intellectual disability. To our knowledge, PUS3 has been postulated only recently as a candidate disease gene for intellectual disability in a single family with three affected siblings. Our findings provide additional evidence to establish loss of PUS3 function as a cause of intellectual disability.

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Section: Introductionmentioning

confidence: 99%

Genetic basis of neurodevelopmental disorders in 103 Jordanian families

et al. 2020

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“…This study adds more information to the previous studies and highlights the importance of early genetic testing of the neurodevelopmental diseases in general because early diagnosis might be beneficial for possible treatments. In Jordan few families who are affected with neurodevelopmental disorders undergo molecular diagnosis 17-22…”

Section: Resultsmentioning

confidence: 99%

Genetic study in a family with dopa-responsive dystonia revealed a novel mutation in sepiapterin reductase gene

Froukh

2019

Pak J Med Sci

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Dopa-responsive dystonia due to sepiapterin reductase deficiency (OMIM#612716) is caused by recessive mutations in the gene encoding sepiapterin reductase (SPR), which plays an important role in the biosynthesis of tetrahydrobiopterin (BH4). One Jordanian patient to first cousin parents is reported in this study. The parents of the proband have recognized the symptoms of their daughter at six months old with motor developmental delay. The symptoms were progressed after-then to include speech delay, seizure, ataxia, oculomotor apraxia, dysarthia and choreoathetosis. Despite of these symptoms, the clinicians in Jordan were unable to diagnose the case. In August 2018, the proband (8 years old) was presented to the department of biotechnology and genetic engineering at Philadelphia University in Jordan for the purposes of performing whole exome sequencing (WES). Analysis of WES data has revealed novel homozygous frameshift variant in the gene SPR (NM_003124.4:c.40delG,p.Ala15Profs*100). The variant is heterozygous in the parents and in the healthy male siblings. Therefore, the studied case was diagnosed with sepiapterin reductase deficiency. Because this disease is likely to be treated recommendations were given to the family immediately to start treatments trials. The case in this study illustrates the difficulties of diagnosing sepiapterin reductase deficiency based on clinical symptoms only and thus renders the possibilities of early management. Also, this study reinforces the importance of running WES to undiagnosed neurodevelopmental cases. doi: https://doi.org/10.12669/pjms.35.6.1181 How to cite this:Froukh T. Genetic study in a family with dopa-responsive dystonia revealed a novel mutation in sepiapterin reductase gene. Pak J Med Sci. 2019;35(6):1736-1739. doi: https://doi.org/10.12669/pjms.35.6.1181 This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/3.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

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“…The initial clinical manifestations of CLN6 disease generally begin between the ages of 2 and 4 years [ 13 ] and are characterized by motor regression, visual loss, the presence of rapid and involuntary muscle movements, and multiple seizures types [ 14 , 15 ]. In advanced stages, patients commonly develop ataxia, further cognitive and motor deterioration, and finally spastic quadriparesia [ 16 , 17 ]. Imaging-based studies commonly find cortical and/or subcortical grey matter atrophy [ 15 , 17 – 19 ] and, like most other forms of NCL, there are no approved disease-modifying treatments.…”

Section: Introductionmentioning

confidence: 99%

“…Mutations in the CLN6 gene are observed mainly in patients of Portuguese, Indian, Pakistani or Czech descent, but have also been documented in countries such as Costa Rica, Sudan, Turkey and Japan [16,[21][22][23]. By the end of the 1990s, studies aimed at identifying and analyzing the most common genetic variant in late infantile NCL began in the Costa Rican population [24][25][26].…”

Section: Introductionmentioning

confidence: 99%

Neuronal Ceroid Lipofuscinosis Type 6 (CLN6) clinical findings and molecular diagnosis: Costa Rica’s experience

Badilla‐Porras

Echeverri-McCandless²,

Weimer

et al. 2022

Orphanet J Rare Dis

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Background Commonly known as Batten disease, the neuronal ceroid lipofuscinoses (NCLs) are a genetically heterogeneous group of rare pediatric lysosomal storage disorders characterized by the intracellular accumulation of autofluorescent material (known as lipofuscin), progressive neurodegeneration, and neurological symptoms. In 2002, a disease-causing NCL mutation in the CLN6 gene was identified (c.214G > T) in the Costa Rican population, but the frequency of this mutation among local Batten disease patients remains incompletely characterized, as do clinical and demographic attributes for this rare patient population. Objective To describe the main sociodemographic and clinical characteristics of patients with a clinical diagnosis for Batten Disease treated at the National Children's Hospital in Costa Rica and to characterize via molecular testing their causative mutations. Methods DNA extracted from buccal swabs was used for CLN6 gene sequencing. Participants’ sociodemographic and clinical characteristics were also obtained from their medical records. Results Nine patients with a clinical diagnosis of Batten disease were identified. Genetic sequencing determined the presence of the previously described Costa Rican homozygous mutation in 8 of 9 cases. One patient did not have mutations in the CLN6 gene. In all cases where the Costa Rican CLN6 mutation was present, it was accompanied by a substitution in intron 2. Patients were born in 4 of the 7 Costa Rican provinces, with an average onset of symptoms close to 4 years of age. No parental consanguinity was present in pedigrees. Initial clinical manifestations varied between patients but generally included: gait disturbances, language problems, visual impairment, seizures and psychomotor regression. Cortical and cerebellar atrophy was a constant finding when neuroimaging was performed. Seizure medication was a common element of treatment regimens. Conclusions This investigation supports that the previously characterized c.214G > T mutation is the most common causative NCL mutation in the Costa Rican population. This mutation is geographically widespread among Costa Rican NCL patients and yields a clinical presentation similar to that observed for CLN6 NCL patients in other geographies.

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Two cases of variant late infantile ceroid lipofuscinosis in Jordan

Cited by 8 publications

References 23 publications

Genetic basis of neurodevelopmental disorders in 103 Jordanian families

Genetic basis of neurodevelopmental disorders in 103 Jordanian families

Genetic study in a family with dopa-responsive dystonia revealed a novel mutation in sepiapterin reductase gene

Neuronal Ceroid Lipofuscinosis Type 6 (CLN6) clinical findings and molecular diagnosis: Costa Rica’s experience

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