Expanding the Phenotypic Spectrum of Alazami Syndrome: Two Unrelated Spanish Families

Gonda, Emma Soengas; Fuente, Rubén Pérez de la; Arteche‐López, Ana; Gomez-Cano, Maria de los Ángeles; Quesada‐Espinosa, Juan Francisco; Milla, Carmen Palma; Rosales, Jose Miguel Lezana; Mayo, Sonia; Calvín, María Teresa Sánchez; Rodrí­guez, Marí­a José; Tomillo, Olalla Sierra; Rufián, Alexandra Juárez; González, Patricia Ramos; Forte, Clara Herrero; Cortés, Maria del Mar Fenollar; Pérez, M.; Ron, A. García; Rodríguez, Olga; Ionescu, Raluca Oancea; García, Marta Moreno

doi:10.1055/a-1947-8411

Cited by 4 publications

(3 citation statements)

References 22 publications

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“… 22 While immunological workups have not been reported in other children with Alazami, there have been a few other reports of children with frequent ear infections and respiratory infections, which could suggest an associated inborn error of immunity. 18 , 23 LARP7 knockdown suppresses intracellular proliferation of intracellular Legionella bacterial infections, the effect on other bacteria more commonly involved in children's illnesses has not been well studied. 24 Further studies are required to link Alazami syndrome with possible humoral immune deficiency.…”

Section: Discussionmentioning

confidence: 99%

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A 2-Year-Old Child with Alazami Syndrome with Newly Reported Findings of Immune Deficiency, Periventricular Nodular Heterotopia, and Stroke; Broadening the Phenotype of Alazami

Fauntleroy-Love,

Wilson,

Padem

et al. 2023

Child Neurology Open

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Alazami syndrome is a rare autosomal recessive neurodevelopmental disorder due to loss-of-function variants in the La ribonucleoprotein 7 (LARP7) gene. Children with Alazami syndrome are most often affected by a combination of primordial dwarfism, intellectual disability, and distinctive facial features. Previous cases have been primarily found in consanguineous families from the Middle East, Asia, and North Africa. We present a 21-month-old Caucasian male from the Midwest United States with nonconsanguineous parents who presented with frequently reported findings of unusual facial features, poor growth, cardiac and genitourinary findings, and developmental delay; less-frequently reported findings, including transient erythroblastopenia of childhood (TEC) and immune deficiency; and never-before reported findings of periventricular nodular heterotopia and stroke. He developed stroke during a hospitalization for Hemophilus influenzae meningitis. The possible contributions of LARP7 to TEC, immune deficiency, brain malformation, and stroke are discussed. Guidelines for the care of Alazami patients are proposed.

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Section: Discussionmentioning

confidence: 99%

“…Epilepsy: Our patient has not had any signs of epilepsy, but epilepsy has been diagnosed in many other cases of Alazami syndrome. 4 , 7 , 17 , 18 , 23 , 25 …”

Section: Discussionmentioning

confidence: 99%

A 2-Year-Old Child with Alazami Syndrome with Newly Reported Findings of Immune Deficiency, Periventricular Nodular Heterotopia, and Stroke; Broadening the Phenotype of Alazami

Fauntleroy-Love,

Wilson,

Padem

et al. 2023

Child Neurology Open

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“…A total of 52 pathogenic variants in the LARP7 gene have been identified in patients with Alazami syndrome 23 . Patients with Alazami syndrome exhibit very short telomeres, and LARP7 knockdown in cancer cells causes a reduction in telomerase activity and telomere shortening 21 .…”

mentioning

confidence: 99%

LARP3, LARP7, and MePCE are Involved in the Early Stage of Human Telomerase RNA Biogenesis

Tseng,

Kao,

Chen

et al. 2023

Preprint

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Human telomerase assembly is a highly dynamic process. Using biochemical approaches, we found that LARP3 and LARP7/MePCE are involved in the early stage and that their binding to hTR is destabilized when the mature hTR is produced. LARP7 and MePCE knockdown inhibits the conversion of the 3′-extended short (exS) form into mature hTR and the cytoplasmic accumulation of hTR, resulting in telomere shortening. LARP3 plays a negative role in preventing the processing of the 3′-extended long (exL) form and binding of LARP7 and MePCE. Interestingly, the tertiary structure of the exL form prevents LARP3 binding and facilitates hTR biogenesis. Supporting this process, LARP3 at low levels promotes hTR maturation, increases telomerase activity, and elongates telomeres. Our data suggest that LARP3 and LARP7/MePCE mediate the processing of hTR precursors and thus control the production of functional telomerase.

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LARP3, LARP7, and MePCE are involved in the early stage of human telomerase RNA biogenesis

Kao,

Huang,

Chen

et al. 2024

Nat Commun

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Human telomerase assembly is a highly dynamic process. Using biochemical approaches, we find that LARP3 and LARP7/MePCE are involved in the early stage of human telomerase RNA (hTR) and that their binding to RNA is destabilized when the mature form is produced. LARP3 plays a negative role in preventing the processing of the 3′-extended long (exL) form and the binding of LARP7 and MePCE. Interestingly, the tertiary structure of the exL form prevents LARP3 binding and facilitates hTR biogenesis. Furthermore, low levels of LARP3 promote hTR maturation, increase telomerase activity, and elongate telomeres. LARP7 and MePCE depletion inhibits the conversion of the 3′-extended short (exS) form into mature hTR and the cytoplasmic accumulation of hTR, resulting in telomere shortening. Taken together our data suggest that LARP3 and LARP7/MePCE mediate the processing of hTR precursors and regulate the production of functional telomerase.

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Expanding the Phenotypic Spectrum of Alazami Syndrome: Two Unrelated Spanish Families

Cited by 4 publications

References 22 publications

A 2-Year-Old Child with Alazami Syndrome with Newly Reported Findings of Immune Deficiency, Periventricular Nodular Heterotopia, and Stroke; Broadening the Phenotype of Alazami

A 2-Year-Old Child with Alazami Syndrome with Newly Reported Findings of Immune Deficiency, Periventricular Nodular Heterotopia, and Stroke; Broadening the Phenotype of Alazami

LARP3, LARP7, and MePCE are Involved in the Early Stage of Human Telomerase RNA Biogenesis

LARP3, LARP7, and MePCE are involved in the early stage of human telomerase RNA biogenesis

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