Alazami syndrome: the first case of papillary thyroid carcinoma

Ivanovski, Ivan; Caraffi, Stefano Giuseppe; Magnani, Elisa; Rosato, Simonetta; Pollazzon, Marzia; Matalonga, Leslie; Piana, Simonetta; Nicoli, Davide; Baldo, Chiara; Bernasconi, Sergio; Frasoldati, Andrea; Zuffardi, Orsetta; Garavelli, Livia

doi:10.1038/s10038-019-0682-5

Cited by 13 publications

(29 citation statements)

References 28 publications

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“…Of the 14 identified variants, 12 were frameshift, one was nonsense, and one was predicted to cause abnormal splicing. Therefore, all deleterious variants causing Alazami syndrome are presumably null alleles [5]. Our findings are in line with the current literature, as the variant detected in our patient is a frameshift predicted to cause the deletion of the last 217 amino acids and, therefore, the loss of the RNA recognition motif 2 (RRM2).…”

Section: Discussionsupporting

confidence: 92%

“…To date, the clinical effect of deleterious variants in LARP7 is restricted to Alazami syndrome. Currently, 24 patients from 12 families are described as having Alazami syndrome and recessive variants in LARP7 [5]. Of the 14 identified variants, 12 were frameshift, one was nonsense, and one was predicted to cause abnormal splicing.…”

Section: Discussionmentioning

confidence: 99%

“…Schematic representation of the protein domains of La-related protein 7[20,21], encoded by LARP7, with positions of all known deleterious variants published to date and including the present one[4,5,19,[22][23][24][25][26] . The variant identified here is in red.…”

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confidence: 99%

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Compound Phenotype Due to Recessive Variants in LARP7 and OTOG Genes Disclosed by an Integrated Approach of SNP-Array and Whole Exome Sequencing

Palumbo

Leone

et al. 2020

Genes

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Neurodevelopmental disorders are a challenge in medical genetics due to genetic heterogeneity and complex genotype-phenotype correlations. For this reason, the resolution of single cases not belonging to well-defined syndromes often requires an integrated approach of multiple whole-genome technologies. Such an approach has also unexpectedly revealed a complex molecular basis in an increasing number of patients, for whom the original suspect of a pleiotropic syndrome has been resolved as the summation effect of multiple genes. We describe a 10-year-old boy, the third son of first-cousin parents, with global developmental delay, facial dysmorphism, and bilateral deafness. SNP-array analysis revealed regions of homozygosity (ROHs) in multiple chromosome regions. Whole-exome sequencing prioritized on gene-mapping into the ROHs showed homozygosity for the likely pathogenic c.1097_1098delAG p. (Arg366Thrfs*2) frameshift substitution in LARP7 and the likely pathogenic c.5743C>T p.(Arg1915*) nonsense variant in OTOG. Recessive variants in LARP7 cause Alazami syndrome, while variants in OTOG cause an extremely rare autosomal recessive form of neurosensorial deafness. Previously unreported features were acrocyanosis and palmoplantar hyperhidrosis. This case highlights the utility of encouraging technological updates in medical genetics laboratories involved in the study of neurodevelopmental disorders and integrating laboratory outputs with the competencies of next-generation clinicians.

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Section: Discussionsupporting

confidence: 92%

Section: Discussionmentioning

confidence: 99%

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Compound Phenotype Due to Recessive Variants in LARP7 and OTOG Genes Disclosed by an Integrated Approach of SNP-Array and Whole Exome Sequencing

Palumbo

Leone

et al. 2020

Genes

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“…Noteworthy, based on clinical findings and presence of peculiar malformations, a diagnosis of SLOS was originally suspected in our siblings ( Table 1). The SLOS phenotypic spectrum is very broad, ranging from a mild disorder with subtle facial dysmorphisms and behavioral and/or learning problems to a prenatally lethal condition (Bianconi et al, 2015;Nowaczyk & Wassif, 1993-2020. Syndactyly of the second and third toes is the most frequent clinical finding in patients with SLOS: its association with growth failure, intellectual disability with autistic traits, and a spectrum of malformations often including corpus callosum and septum pellucidum anomalies, congenital heart defects, and hypospadias should prompt testing for this condition (Lee, Conley, Gropman, Porter, & Baker, 2013;Nowaczyk & Irons, 2012;Porter, 2008).…”

Section: Discussionmentioning

confidence: 99%

“…To date, 24 affected patients, belonging to 12 families, have been reported, all sharing a core of recognizable features: (a) short stature bordering in some cases with primordial dwarfism; (b) moderate to severe global developmental delay/intellectual disability (GDD/ID); (c) peculiar dysmorphisms, including prominent forehead, deep‐set eyes, malar hypoplasia, broad nose, wide mouth, and widely spaced teeth. Other findings such as microcephaly, congenital heart defects, and autistic/maladaptive behaviors have been reported in about half cases (Alazami et al, 2012; Dateki et al, 2018; Elmas et al, 2019; Hollink et al, 2016; Holohan et al, 2016; Imbert‐Bouteille et al, 2019; Ivanovski et al, 2020; Karaca et al, 2015; Ling & Sorrentino, 2016; Najmabadi et al, 2011; Wojcik, Linnea, Stoler, & Rappaport, 2019).…”

Section: Introductionmentioning

confidence: 99%

Alazami syndrome: Phenotypic expansion and clinical resemblance to Smith–Lemli–Opitz syndrome

Gana¹,

Plumari²,

Rossi

et al. 2020

American J of Med Genetics Pt A

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Biallelic mutations in the LARP7 gene have been recently shown to cause Alazami syndrome, a rare condition characterized by short stature, intellectual disability, and peculiar facial dysmorphisms. To date, only 24 cases have been reported. Here, we describe two brothers initially suspected to have Smith-Lemli-Opitz syndrome, in whom clinical exome sequencing detected a novel homozygous truncating variant in LARP7. These cases expand the phenotypic spectrum of Alazami syndrome to include toes syndactyly and adaptive behavior, and confirm the power of "genotype first" approach in patients with syndromic presentations overlapping distinct rare conditions.

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Alazami syndrome: Report of three Indian patients with phenotypic spectrum from adolescence to adulthood

Das

Godbole

Abraham

et al. 2021

American J of Med Genetics Pt A

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Alazami syndrome (ALAZS) (MIM 615071) is a rare autosomal recessive disorder characterized by short stature, dysmorphic facial features, developmental delay, and impaired intellect. It was first reported in a Saudi Arabian family in 2012. Three Indian patients affected with ALAZS, one boy aged 13 years and other two sisters in their 40s are presented. These patients had few unreported dysmorphic facial features: high arched eyebrows and dental overcrowding. No microcephaly was noted in the sisters. One of the sisters did not have short stature. The boy also presented with unilateral buphthalmos of left eye. All three of them have been identified to harbor novel variants in LARP7.

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Alazami syndrome: the first case of papillary thyroid carcinoma

Cited by 13 publications

References 28 publications

Compound Phenotype Due to Recessive Variants in LARP7 and OTOG Genes Disclosed by an Integrated Approach of SNP-Array and Whole Exome Sequencing

Compound Phenotype Due to Recessive Variants in LARP7 and OTOG Genes Disclosed by an Integrated Approach of SNP-Array and Whole Exome Sequencing

Alazami syndrome: Phenotypic expansion and clinical resemblance to Smith–Lemli–Opitz syndrome

Alazami syndrome: Report of three Indian patients with phenotypic spectrum from adolescence to adulthood

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