Prenatal diagnosis of a nonsense mutation in the L1CAM gene resulting in congenital hydrocephalus: A case report and literature review

Wang, Rongyue; Chen, Hua; Wang, Xiaona; Huang, Sisi; Xie, Anmu; Wu, Xinmei

doi:10.3892/etm.2021.10807

Cited by 6 publications

(6 citation statements)

References 35 publications

(73 reference statements)

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“…Cases of consecutive abortions and miscarriages have been reported in in casestudies. 14,15 Likewise this study was also able to observe a significant association (p-value 0.014) of family history in 55.6% (20 cases). Out of these 9 cases exhibited fetal hydrocephalus due to consanguinity.…”

Section: Discussionsupporting

confidence: 73%

“…16 Non-sense, missense and frameshift mutations have been observed in association with fetal X-linked hydrocephalus in male fetuses. 14,17 Authors have identified MPDZ mutation, TRIM 1, SMARCC 1, PTCH, SHH and POMT2 in association with congenital hydrocephalus in male fetuses with or without any positive family history. 18,19 In a case-control study in Ethiopia, only 2 cases of enlarged fetal ventricular system were reported to be associated with consanguinity.…”

Section: Discussionmentioning

confidence: 99%

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A study relating fetal hydrocephalus with family history and consanguinity in Pakistani population.

Surti¹,

Usmani²,

Javaid³

2023

TPMJ

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Objective: To correlate the amniotic fluid index (AFI), measurements of biparietal diameter (BPD) and head circumference (HC) with atrium of lateral ventricle measurements (ALV) and relate the association of fetal hydrocephalus with family history and consanguinity. Study Design: Cross-sectional study. Setting: Private Ultrasound Clinic, Karachi. Period: December 2018 – July 2019. Material & Methods: Thirty six patients were inducted in the study. Female patients of age range of 18-41 years with gestational age of 21-39 weeks were inducted into the study after informed consent. Toshiba Aplio 300 ultrasound machine was used to measure, atrium of lateral ventricle, biparietal diameter, fetal length, head circumference and amniotic fluid index. Association between ALV and BPD, family history and consanguinity was seen by applying independent t-test while Pearson’s correlation was used to correlate the measurements of ALV and head circumference. Results: Atrium of lateral ventricle measurements >10mm were diagnosed as hydrocephalus. It was observed that hydrocephalus was associated with normal volumes of amniotic fluid with highly significant results (<0.000). Furthermore, the study also reported a strong association of family history and consanguineous marriages with hydrocephalus. A negative correlation was however observed between measurements of atrium of lateral ventricle and head circumference. Conclusion: Hydrocephalus was found to be associated with normal volumes of amniotic flid and had a strong association with family history and consanguinity.

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Section: Discussionsupporting

confidence: 73%

Section: Discussionmentioning

confidence: 99%

A study relating fetal hydrocephalus with family history and consanguinity in Pakistani population.

Surti¹,

Usmani²,

Javaid³

2023

TPMJ

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“… 15 It has been reported that missense mutations are subdivided as “key amino acid residues” and “surface residues.” The missense mutations which affect “key amino acid residues” are located in the extracellular part of L1CAM resulting in the diminution of both homophilic and 3 heterophilic bindings and this might produce more severe neurological problems. 16 , 17 Since the variant (Tyr784Cys) presented here, located in the second Fn domain, is required for homophilic binding, it is defined as key residue mutation.…”

Section: Discussionmentioning

confidence: 99%

Severe Phenotype in Patients with X-linked Hydrocephalus Caused by a Missense Mutation in L1CAM

Tüysüz¹,

Sencicek²,

Özer³

et al. 2022

Turk Arch Pediatrics

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Objective: The study aimed to show the clinical characteristics and prognosis of the L1 syndrome in patients with L1CAM mutations in the extracellular region. Materials and Methods: Three affected boys and their siblings and parents from a large family were included in this study. Genetic etiology was investigated by whole-exome sequencing in the index patient. The pathogenic variant was detected by whole-exome sequencing and was validated by Sanger sequencing in 3 patients and other family members. Results: We present 2 brothers and their cousin with prenatal onset hydrocephalus, severe developmental and speech delay, corpus callosum agenesis/hypogenesis, epilepsia, and adducted thumbs. A hemizygous missense mutation NM_024003 (c.A2351G:p.Y784C) on exon 18 of L1CAM gene was found in the 3 patients and their carrier mother. This missense mutation in the conserved region of the second fibronectin type III-like repeats located in the extracellular region of L1CAM resulted in the severe phenotype of X-linked inherited L1 syndrome in the patients. Conclusion: L1 syndrome should be considered in the differential diagnosis of male children with intellectual disability, hydrocephalus, and adducted thumbs. While truncating mutations of L1CAM may cause a more severe phenotype, missense mutations cause milder forms. However, pathogenic missense mutations affecting key amino acid residues lead to severe phenotype likely.

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“…It is estimated that up to 40% of cases of hydrocephalus refer to a possible genetic etiology ( Haverkamp et al, 1999 ), and over 100 genes have been described to be mutated in syndromic hydrocephalus cases ( Kousi and Katsanis, 2016 ). Thereinto, X-linked hydrocephalus comprises about 5–15% of genetic-related congenital hydrocephalus ( Haverkamp et al, 1999 ; Zhang et al, 2006 ; Adle-Biassette et al, 2013 ), and bona fide mutations have been described in four genes, that is, L1 cell adhesion molecule ( L1CAM ), sigma 2 subunit of the adapter protein 1 complex ( AP1S2 ), multiple PDZ domain proteins ( MPDZ ), and coiled-coil domain-containing protein 88c ( CCDC88C ) ( Tarpey et al, 2006 ; Al-Dosari et al, 2013 ; Shaheen et al, 2017 ; Yang et al, 2019 ; Etchegaray et al, 2020 ; Marguet et al, 2021 ; Wang et al, 2021 ). Since the phenotypes are heterogenic, there may be more genetic loci in congenital hydrocephalus.…”

Section: Human Genetic Studies Of Hydrocephalusmentioning

confidence: 99%

Molecular Mechanisms and Risk Factors for the Pathogenesis of Hydrocephalus

Zhang

Guo

et al. 2022

Front. Genet.

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Hydrocephalus is a neurological condition due to the aberrant circulation and/or obstruction of cerebrospinal fluid (CSF) flow with consequent enlargement of cerebral ventricular cavities. However, it is noticed that a lot of patients may still go through symptomatic progression despite standard shunting procedures, suggesting that hydrocephalus is far more complicated than a simple CSF circulative/obstructive disorder. Growing evidence indicates that genetic factors play a fundamental role in the pathogenesis of some hydrocephalus. Although the genetic research of hydrocephalus in humans is limited, many genetic loci of hydrocephalus have been defined in animal models. In general, the molecular abnormalities involved in the pathogenesis of hydrocephalus include brain development and ependymal cell dysfunction, apoptosis, inflammation, free radical generation, blood flow, and cerebral metabolism. Moreover, recent studies have indicated that the molecular abnormalities relevant to aberrant cerebral glymphatic drainage turn into an attractive subject in the CSF circulation disorder. Furthermore, the prevalent risk factors could facilitate the development of hydrocephalus. In this review, we elicited some possible fundamental molecular mechanisms and facilitating risk factors involved in the pathogenesis of hydrocephalus, and aimed to widen the diagnosis and therapeutic strategies for hydrocephalus management. Such knowledge could be used to improve patient care in different ways, such as early precise diagnosis and effective therapeutic regimens.

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Prenatal diagnosis of a nonsense mutation in the L1CAM gene resulting in congenital hydrocephalus: A case report and literature review

Cited by 6 publications

References 35 publications

A study relating fetal hydrocephalus with family history and consanguinity in Pakistani population.

A study relating fetal hydrocephalus with family history and consanguinity in Pakistani population.

Severe Phenotype in Patients with X-linked Hydrocephalus Caused by a Missense Mutation in L1CAM

Molecular Mechanisms and Risk Factors for the Pathogenesis of Hydrocephalus

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