Whole exome sequencing uncovered highly penetrant recessive mutations for a spectrum of rare genetic pediatric diseases in Bangladesh

Akter, Hosneara; Hossain, Mohammad Shahnoor; Dity, Nushrat Jahan; Rahaman, Md. Atikur; Uddin, K. M. Furkan; Nassir, Nasna; Begum, Ghausia; Hameid, Reem Abdel; Islam, Mohammad Shaiful; Tusty, Tahrima Arman; Basiruzzaman, Mohammad; Sarkar, Shaoli; Islam, Mazharul; Jahan, Sharmin; Lim, Elaine T.; Woodbury‐Smith, Marc; Stavropoulos, Dimitri J.; O’Rielly, Darren D.; Berdeiv, Bakhrom K.; Nabi, A.H.M. Nurun; Ahsan, Mohammed Nazmul; Scherer, Stephen W.; Uddin, Mohammed

doi:10.1038/s41525-021-00173-0

Cited by 12 publications

(10 citation statements)

References 67 publications

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“…Whole-genome sequencing has been done for only four Bangladeshi individuals, revealing over 11,500 variants responsible for different diseases and 17 genetic diseases [11] . Another whole-exome sequencing study discovered the presence of pathogenic variants in other genes associated with an extremely rare genetic diseases in five unrelated patients [12] .…”

Section: Status Of Genetic Disease Research In Bangladeshmentioning

confidence: 99%

Constructing human genetic disease database in Bangladesh

Akter¹,

Araf²,

Anwar³

et al. 2022

Gene Protein Dis

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In the advent of technological revolution, genetic interaction has become a crucial aspect in the understanding of any diseases. Information on individual genetic variation is now used in translational genomics to implement precise diagnosis and personalized medicine. Finding causal genes for genetic diseases or exploring interaction of genes in diseases with genetic predisposition is the first step to getting insights into such diseases. The human genome project made a paradigm shift in thinking, especially in the developed countries affected by non-communicable diseases. Some cutting-edge technologies, including gene therapy and genome editing, hold the promise in better diagnosis and treatment of common to rare genetic diseases. Scientific communities are trying hard to accumulate all the genetic disease information from publicly available platforms. A genetic disease database of a country serves as a depository. Many developed and a few developing countries have already developed genetic disease databases, which could benefit early diagnosis and proper patient management. Unfortunately, Bangladesh is lagging behind in this aspect. It is imperative to develop genetic disease database in Bangladesh because of its large population of patients with genetic disease. In this review, we discuss the reasons for constructing a genetic disease database and how this database can help to fight against challenges arising from the genetic diseases in Bangladesh.

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Section: Status Of Genetic Disease Research In Bangladeshmentioning

confidence: 99%

Constructing human genetic disease database in Bangladesh

Akter¹,

Araf²,

Anwar³

et al. 2022

Gene Protein Dis

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“…Our searches were based on combinations of the following index terms: DHH , 46, XY gonadal dysplasia, 46, XY gonadal dysgenesis, 46, XY disorder of sex development, neuropathy, Hedgehog signaling pathway and the corresponding terms in Chinese. A total of 25 cases of DHH variants causing 46, XY GD in detail have been reported worldwide so far ( Umehara et al, 2000 ; Canto et al, 2004 ; Das et al, 2011 ; Werner et al, 2015 ; Paris et al, 2017 ; Sato et al, 2017 ; Baldinotti et al, 2018 ; Rothacker et al, 2018 ; Tajouri et al, 2018 ; Ayers et al, 2019 ; Buonocore et al, 2019 ; Neocleous et al, 2019 ; Akter et al, 2021 ; Kalinchenko et al, 2021 ; Mehta et al, 2021 ) (see Table 2 ), including 24 different variant types of missense, deletion, duplication, or transversion, and both homozygous and compound heterozygous variants have been reported. The reported ages ranged from 2.8 to 55 years.…”

Section: Case Presentationmentioning

confidence: 99%

Case Report: Long-term follow-up of desert hedgehog variant caused 46, XY gonadal dysgenesis with multiple complications in a Chinese child

Pan

et al. 2022

Front. Genet.

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Background: Desert hedgehog (DHH), as a member of the Hedgehog (HH) family, is mainly involved in testicular development and peripheral nerve sheath formation. A DHH variant has been identified in patients with 46, XY gonadal dysgenesis (46, XY GD) with or without neuropathy, but few reports mention the involvement of other complications.Case presentation: Here, we report a Chinese female patient who was hospitalized at 14.3 years old due to slow breast development for more than 1 year. She had a female genitalia phenotype and breast development started at 13 years old but progressed slowly. She was not yet menarche on admission, and she had intermittent muscle cramps in her hands and feet. Her karyotype analysis was 46, XY and the SRY gene was positive. Surgical exploration revealed no uterus or ovaries, and the pathology of bilateral gonads was dysplastic testis tissue, which was consistent with partial gonadal dysgenesis (PGD). Genetic analysis identified a homozygous pathogenic variant in DHH exon 3 (c.1027T>C, p. Cys343Arg). During the 6-year follow-up, she received estrogen replacement therapy, resulting in breast development progression without gender dysphoria. However, her peripheral neuropathy became more obvious, and a nerve conduction study (NCS) indicated decreased nerve conduction velocity and action potential. In addition, she also suffered complications such as obesity, insulin resistance, fatty liver, and gastric ulcers.Conclusion: In the present study, we reported a case of 46, XY GD with minifascicular neuropathy caused by a DHH homozygous variant, and we summarized the reported cases worldwide. For the first time in such patients, we showed a comparison of NCS changes with age as well as the presence of multiple complications not previously reported.

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“…Позже были описаны пациенты без МФПНП и с различными вариантами ДГ (чистая ДГ, смешанная ДГ). Среди описанных случаев патологические замены в гене DHH располагались во всех трех экзонах, без какой-либо преимущественной локализации [10][11][12].…”

Section: высококонсервативноеunclassified

Clinical Findings in Two patients with DSD 46XY caused by new variant of the <i>Desert Hedgehog</i> Gene and review of the literature of the role of DHH signaling pathway in sex development

Kalinchenko

Batyrova²,

Коstrova³

et al. 2021

Probl Endokrinol (Mosk)

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Mutations in the gene DHH are an extremely rare cause of disorders of sex development 46,XY (DSD,46XY). The article describes the clinical cases of two unrelated patients with gonadal dysgenesis 46,XY with female phenotype. By using a next generation sequencing method, in both cases the same biallelic variant substitution c. 419T>G in the DHH gene was revealed. Taking into account the data on the role of DHH in the formation of the nervous system, the diagnosis of minifascicular polyneuropathy at the preclinical stage was confirmed in both cases. These cases demonstrate the value of using NGS, which allows simultaneous analysis of a wide range of candidate genes in DSD and the diagnosis of comorbidities before the development of the clinical picture. These are the first descriptions of patients with mutations in the DHH gene in the Russian population.

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Whole exome sequencing uncovered highly penetrant recessive mutations for a spectrum of rare genetic pediatric diseases in Bangladesh

Cited by 12 publications

References 67 publications

Constructing human genetic disease database in Bangladesh

Constructing human genetic disease database in Bangladesh

Case Report: Long-term follow-up of desert hedgehog variant caused 46, XY gonadal dysgenesis with multiple complications in a Chinese child

Clinical Findings in Two patients with DSD 46XY caused by new variant of the <i>Desert Hedgehog</i> Gene and review of the literature of the role of DHH signaling pathway in sex development

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