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Immunodeficiency in a patient with microcephalic osteodysplastic primordial dwarfism type I as compared to Roifman syndrome.
Brain Dev. 2021 Feb; 43(2):337-342.BD

Abstract

BACKGROUND

Microcephalic osteodysplastic primordial dwarfism type I (MOPD I, also known as Taybi-Linder syndrome) is a rare genetic disorder associated with severe intrauterine growth retardation, short stature, microcephaly, brain anomalies, stunted limbs, and early mortality. RNU4ATAC, the gene responsible for this disorder, does not encode a protein but instead the U4atac small nuclear RNA (snRNA), a crucial component of the minor spliceosome. Roifman syndrome is an allelic disorder of MOPD I that is characterized by immunodeficiency complications.

CASE REPORT

The patient described herein is an 18-year-old woman exhibiting congenital dwarfism and microcephaly with structural brain anomaly. She suffered human herpesvirus 6 (HHV-6)-associated acute necrotizing encephalopathy at the age of one, thereafter resulting in severe psychomotor disabilities. Genetic analysis using gene microarray and whole-exome sequencing could not identify the cause of her congenital anomalies. However, Sanger sequencing revealed a compound heterozygous mutation within RNU4ATAC (NR_023343.1:n.[50G > A];[55G > A]). Immunological findings showed decreases in total lymphocytes, CD4+ T cells, and T cell regenerative activity. Furthermore, antibodies against varicella-zoster, rubella, measles, mumps, and influenza were very low or negative despite having received vaccinations for these viruses. HHV-6 IgG antibodies were also undetected.

DISCUSSION

The patient here exhibited a marked MOPD I phenotype complicated by various immunodeficiencies. Previous studies have not demonstrated immunodeficiency comorbidities within MOPD I subjects, but this report suggests an evident immunodeficiency in MOPD I. Patients with MOPD I should be treated with one of the immunodeficiency syndromes.

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Authors+Show Affiliations

Department of Pediatrics, National Defense Medical College Hospital, 3-2 Namiki, Tokorozawa, Saitama 359-8513, Japan.

Department of Pediatrics, National Defense Medical College Hospital, 3-2 Namiki, Tokorozawa, Saitama 359-8513, Japan. Electronic address: matumoto@ndmc.ac.jp.

Department of Pediatrics, National Defense Medical College Hospital, 3-2 Namiki, Tokorozawa, Saitama 359-8513, Japan.

Department of Pediatrics, National Defense Medical College Hospital, 3-2 Namiki, Tokorozawa, Saitama 359-8513, Japan.

Department of Pediatrics, National Defense Medical College Hospital, 3-2 Namiki, Tokorozawa, Saitama 359-8513, Japan.

Department of Human Genetics, Yokohama City University Graduate School of Medicine, Fukuura 3-9, Kanazawa-ku, Yokohama 236-0004, Japan.

Department of Human Genetics, Yokohama City University Graduate School of Medicine, Fukuura 3-9, Kanazawa-ku, Yokohama 236-0004, Japan.

Department of Pediatrics, National Defense Medical College Hospital, 3-2 Namiki, Tokorozawa, Saitama 359-8513, Japan.

MeSH

AdolescentAllelesCardiomyopathiesDwarfismFemaleFetal Growth RetardationHumansMental Retardation, X-LinkedMicrocephalyMutationOsteochondrodysplasiasPedigreePhenotypePrimary Immunodeficiency DiseasesRNA, Small NuclearRetinal DiseasesWhole Exome Sequencing

Pub Type(s)

Case Reports

Language

eng

PubMed ID

33059947

Citation

Hagiwara, Hidetoshi, et al. "Immunodeficiency in a Patient With Microcephalic Osteodysplastic Primordial Dwarfism Type I as Compared to Roifman Syndrome." Brain & Development, vol. 43, no. 2, 2021, pp. 337-342.

Hagiwara H, Matsumoto H, Uematsu K, et al. Immunodeficiency in a patient with microcephalic osteodysplastic primordial dwarfism type I as compared to Roifman syndrome. Brain Dev. 2021;43(2):337-342.

Hagiwara, H., Matsumoto, H., Uematsu, K., Zaha, K., Sekinaka, Y., Miyake, N., Matsumoto, N., & Nonoyama, S. (2021). Immunodeficiency in a patient with microcephalic osteodysplastic primordial dwarfism type I as compared to Roifman syndrome. Brain & Development, 43(2), 337-342. https://doi.org/10.1016/j.braindev.2020.09.007

Hagiwara H, et al. Immunodeficiency in a Patient With Microcephalic Osteodysplastic Primordial Dwarfism Type I as Compared to Roifman Syndrome. Brain Dev. 2021;43(2):337-342. PubMed PMID: 33059947.

* Article titles in AMA citation format should be in sentence-case

TY - JOUR T1 - Immunodeficiency in a patient with microcephalic osteodysplastic primordial dwarfism type I as compared to Roifman syndrome. AU - Hagiwara,Hidetoshi, AU - Matsumoto,Hiroshi, AU - Uematsu,Kenji, AU - Zaha,Kiyotaka, AU - Sekinaka,Yujin, AU - Miyake,Noriko, AU - Matsumoto,Naomichi, AU - Nonoyama,Shigeaki, Y1 - 2020/10/12/ PY - 2020/03/31/received PY - 2020/09/08/revised PY - 2020/09/13/accepted PY - 2020/10/17/pubmed PY - 2021/10/6/medline PY - 2020/10/16/entrez KW - Corpus callosum dysgenesis KW - Immunodeficiency KW - Microcephalic osteodysplastic primordial dwarfism type I (MOPD I) KW - Pachygyria KW - RNU4ATAC KW - Roifman syndrome SP - 337 EP - 342 JF - Brain & development JO - Brain Dev VL - 43 IS - 2 N2 - BACKGROUND: Microcephalic osteodysplastic primordial dwarfism type I (MOPD I, also known as Taybi-Linder syndrome) is a rare genetic disorder associated with severe intrauterine growth retardation, short stature, microcephaly, brain anomalies, stunted limbs, and early mortality. RNU4ATAC, the gene responsible for this disorder, does not encode a protein but instead the U4atac small nuclear RNA (snRNA), a crucial component of the minor spliceosome. Roifman syndrome is an allelic disorder of MOPD I that is characterized by immunodeficiency complications. CASE REPORT: The patient described herein is an 18-year-old woman exhibiting congenital dwarfism and microcephaly with structural brain anomaly. She suffered human herpesvirus 6 (HHV-6)-associated acute necrotizing encephalopathy at the age of one, thereafter resulting in severe psychomotor disabilities. Genetic analysis using gene microarray and whole-exome sequencing could not identify the cause of her congenital anomalies. However, Sanger sequencing revealed a compound heterozygous mutation within RNU4ATAC (NR_023343.1:n.[50G > A];[55G > A]). Immunological findings showed decreases in total lymphocytes, CD4+ T cells, and T cell regenerative activity. Furthermore, antibodies against varicella-zoster, rubella, measles, mumps, and influenza were very low or negative despite having received vaccinations for these viruses. HHV-6 IgG antibodies were also undetected. DISCUSSION: The patient here exhibited a marked MOPD I phenotype complicated by various immunodeficiencies. Previous studies have not demonstrated immunodeficiency comorbidities within MOPD I subjects, but this report suggests an evident immunodeficiency in MOPD I. Patients with MOPD I should be treated with one of the immunodeficiency syndromes. SN - 1872-7131 UR - https://www.unboundmedicine.com/medline/citation/33059947/Immunodeficiency_in_a_patient_with_microcephalic_osteodysplastic_primordial_dwarfism_type_I_as_compared_to_Roifman_syndrome_ L2 - https://linkinghub.elsevier.com/retrieve/pii/S0387-7604(20)30270-9 DB - PRIME DP - Unbound Medicine ER -