Case Report
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X-Linked Intellectual Disability with NEXMIF Gene Mutation and Developmental Delay with GNAO1 Gene Mutation: Case Report

Year 2024, Volume: 7 Issue: 3, 177 - 182, 31.10.2024
https://doi.org/10.55517/mrr.1439712

Abstract

X-linked intellectual disability (XLID) is a genetically heterogeneous disorder. Currently, 162 genes linked to XLID have been found, but the cause of XLID is still unclear. While the GNAO1 gene is crucial for hypotonia, epilepsy, developmental delay, and movement disorders, the NEXMIF gene, also known as KIAA2022, has associations with XLID, autism, and epilepsy. The subject of the study, a 5-year-old girl has lots of congenital defects, including a cleft palate, anal atresia, hypotonia in her lower limbs, and thumb missing. A variety of eye abnormalities, such as scoliosis, finger malformations, and craniofacial dysmorphism. Radiological tests revealed substantial heart problems, bilateral renal hypoplasia, and brain abnormalities. She met milestones more later than her contemporaries, indicating clear developmental deficits. The NEXMIF and GNAO1 genes both include heterozygous frameshift variants that were discovered through genetic research using next-generation sequencing. The complex and varied clinical signs of XLID are shown in this case. The clinical picture is further complicated by the co-occurrence of mutations in the NEXMIF and GNAO1 genes, which emphasizes the need for an approach to offer suitable therapy solutions. Future studies are necessary to understand the complex interactions between these genes and how they affect XLID and related symptoms.

References

  • Voineagu I, Huang L, Winden K, Lazaro M, Haan E, Nelson J, et al. CCDC22: a novel candidate gene for syndromic X-linked intellectual disability. Mol. Psychiatry. 2012;17(1):4-7.
  • Schwartz CE, Louie RJ, Toutain A, Skinner C, Friez MJ, Stevenson RE. X-Linked intellectual disability update 2022. Am. J. Med. Genet. A. 2023;191(1):144-159.
  • Wang L, Huang Y, Liu X. NEXMIF pathogenic variant in a female child with epilepsy and multiple organ failure: a case report. Transl. Pediatr.2023;12(6):1278.
  • Stamberger H, Hammer TB, Gardella E, Vlaskamp DR, Bertelsen B, Mandelstam S, et al. NEXMIF encephalopathy: an X-linked disorder with male and female phenotypic patterns. Genet. Med. 2021;23(2):363-373.
  • Marcé-Grau A, Dalton J, López-Pisón J, García-Jiménez MC, Monge-Galindo L, Cuenca-León E, et al. GNAO1 encephalopathy: further delineation of a severe neurodevelopmental syndrome affecting females. Orphanet J. Rare Dis. 2016;11(1):1-9.
  • Wirth T, Garone G, Kurian MA, Piton A, Millan F, Telegrafi A, et al. Highlighting the dystonic phenotype related to GNAO1. Mov. Disord. 2022;37(7): 1547-1554.
  • Cantagrel V, Lossi AM, Boulanger S, Depetris D, Mattei MG, Gecz J, et al. Disruption of a new X-linked gene highly expressed in the brain in a family with two mentally retarded males. J. Med. Genet. 2004;41(10):736-742.
  • Panda PK, Sharawat IK, Joshi K, Dawman L, Bolia R. Clinical spectrum of KIAA2022/NEXMIF pathogenic variants in males and females: Report of three patients from Indian kindred with a review of published patients. Brain Dev. 2020;42(9): 646-654.
  • de Lange IM, Helbig KL, Weckhuysen S, Møller RS, Velinov M, Dolzhanskaya N, et al. De novo mutations of KIAA2022 in females cause intellectual disability and intractable epilepsy. J. Med. Genet. 2016;53(12):850-858.
  • Van Maldergem L, Hou Q, Kalscheuer VM, Rio M, Doco-Fenzy M, Medeira A, et al. Loss of function of KIAA2022 causes mild to severe intellectual disability with an autism spectrum disorder and impairs neurite outgrowth. Hum. Mol. Genet. 2013;22(16):3306-3314.

NEXMIF ve GNAO1 Gen Mutasyonlarıyla X'e Bağlı Zihinsel Engellilik: Vaka Sunumu

Year 2024, Volume: 7 Issue: 3, 177 - 182, 31.10.2024
https://doi.org/10.55517/mrr.1439712

Abstract

X'e bağlı zihinsel engellilik (XLID) genetik olarak heterojen bir bozukluktur. Şu anda XLID ile bağlantılı 162 gen bulundu, ancak XLID'nin nedeni hala belirsiz. GNAO1 geni hipotoni, epilepsi, gelişimsel gecikme ve hareket bozuklukları için önemli olsa da, KIAA2022 olarak da bilinen NEXMIF geni XLID, otizm ve epilepsi ile ilişkilidir. Çalışmanın konusu olan 5 yaşında bir kız çocuğunun yarık damak, anal atrezi, alt ekstremitelerinde hipotoni ve baş parmağının olmaması gibi birçok doğuştan kusuru vardır. Skolyoz, parmak malformasyonları ve kraniyofasiyal dismorfizm gibi çeşitli göz anormallikleri vardır. Radyolojik testler önemli kalp sorunları, bilateral böbrek hipoplazisi ve beyin anormallikleri ortaya koydu. Çağdaşlarından daha geç dönüm noktalarına ulaştı ve bu da açık gelişimsel eksiklikleri gösteriyor. NEXMIF (NM_001008537.2) ve GNAO1 (NM_138736.2) genleri, yeni nesil dizileme kullanılarak genetik araştırma yoluyla keşfedilen heterozigot çerçeve kayması varyantlarını içerir. Bu vakada XLID ve gelişimsel gecikmenin karmaşık ve çeşitli klinik belirtileri gösterilmiştir. Klinik tablo, NEXMIF ve GNAO1 genlerindeki mutasyonların birlikte görülmesiyle daha da karmaşık hale gelir ve bu da uygun tedavi çözümleri sunmak için bir yaklaşıma olan ihtiyacı vurgular. Bu genler arasındaki karmaşık etkileşimleri ve XLID ve gelişimsel gecikmeyle ilişkili semptomları nasıl etkilediklerini anlamak için gelecekteki çalışmalara ihtiyaç vardır.

References

  • Voineagu I, Huang L, Winden K, Lazaro M, Haan E, Nelson J, et al. CCDC22: a novel candidate gene for syndromic X-linked intellectual disability. Mol. Psychiatry. 2012;17(1):4-7.
  • Schwartz CE, Louie RJ, Toutain A, Skinner C, Friez MJ, Stevenson RE. X-Linked intellectual disability update 2022. Am. J. Med. Genet. A. 2023;191(1):144-159.
  • Wang L, Huang Y, Liu X. NEXMIF pathogenic variant in a female child with epilepsy and multiple organ failure: a case report. Transl. Pediatr.2023;12(6):1278.
  • Stamberger H, Hammer TB, Gardella E, Vlaskamp DR, Bertelsen B, Mandelstam S, et al. NEXMIF encephalopathy: an X-linked disorder with male and female phenotypic patterns. Genet. Med. 2021;23(2):363-373.
  • Marcé-Grau A, Dalton J, López-Pisón J, García-Jiménez MC, Monge-Galindo L, Cuenca-León E, et al. GNAO1 encephalopathy: further delineation of a severe neurodevelopmental syndrome affecting females. Orphanet J. Rare Dis. 2016;11(1):1-9.
  • Wirth T, Garone G, Kurian MA, Piton A, Millan F, Telegrafi A, et al. Highlighting the dystonic phenotype related to GNAO1. Mov. Disord. 2022;37(7): 1547-1554.
  • Cantagrel V, Lossi AM, Boulanger S, Depetris D, Mattei MG, Gecz J, et al. Disruption of a new X-linked gene highly expressed in the brain in a family with two mentally retarded males. J. Med. Genet. 2004;41(10):736-742.
  • Panda PK, Sharawat IK, Joshi K, Dawman L, Bolia R. Clinical spectrum of KIAA2022/NEXMIF pathogenic variants in males and females: Report of three patients from Indian kindred with a review of published patients. Brain Dev. 2020;42(9): 646-654.
  • de Lange IM, Helbig KL, Weckhuysen S, Møller RS, Velinov M, Dolzhanskaya N, et al. De novo mutations of KIAA2022 in females cause intellectual disability and intractable epilepsy. J. Med. Genet. 2016;53(12):850-858.
  • Van Maldergem L, Hou Q, Kalscheuer VM, Rio M, Doco-Fenzy M, Medeira A, et al. Loss of function of KIAA2022 causes mild to severe intellectual disability with an autism spectrum disorder and impairs neurite outgrowth. Hum. Mol. Genet. 2013;22(16):3306-3314.
There are 10 citations in total.

Details

Primary Language English
Subjects Pediatric Urology
Journal Section Case Reports
Authors

Tayfun Aygün 0000-0001-5058-3513

Sevim Yener 0000-0002-7327-8228

Nurullah Yücel 0000-0003-2689-4287

Gulam Hekimoğlu 0000-0002-5027-6756

Metin Eser 0000-0001-7118-7958

Zekeriya İlce 0000-0002-3473-5051

Early Pub Date October 30, 2024
Publication Date October 31, 2024
Submission Date February 19, 2024
Acceptance Date October 4, 2024
Published in Issue Year 2024 Volume: 7 Issue: 3

Cite

Vancouver Aygün T, Yener S, Yücel N, Hekimoğlu G, Eser M, İlce Z. X-Linked Intellectual Disability with NEXMIF Gene Mutation and Developmental Delay with GNAO1 Gene Mutation: Case Report. MRR. 2024;7(3):177-82.