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Expanding OBSL1 Mutation Phenotype: Disproportionate Short Stature, Barrel Chest, Thoracic Kyphoscoliosis, Hypogonadism, and Hypospadias

We present a Pakistani kinship afflicted with a syndrome with features including short stature, reduced sitting height, orofacial symptoms including prominent forehead and thick eyebrows, short and broad thorax, and variable features such as long philtrum, short broad neck, barrel chest, thoracic ky...

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Autores principales: Koprulu, Mine, Shabbir, Rana Muhammad Kamran, Mumtaz, Sara, Tolun, Aslıhan, Malik, Sajid
Formato: Online Artículo Texto
Lenguaje:English
Publicado: YJBM 2023
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10524810/
https://www.ncbi.nlm.nih.gov/pubmed/37780995
http://dx.doi.org/10.59249/RLAU6003
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author Koprulu, Mine
Shabbir, Rana Muhammad Kamran
Mumtaz, Sara
Tolun, Aslıhan
Malik, Sajid
author_facet Koprulu, Mine
Shabbir, Rana Muhammad Kamran
Mumtaz, Sara
Tolun, Aslıhan
Malik, Sajid
author_sort Koprulu, Mine
collection PubMed
description We present a Pakistani kinship afflicted with a syndrome with features including short stature, reduced sitting height, orofacial symptoms including prominent forehead and thick eyebrows, short and broad thorax, and variable features such as long philtrum, short broad neck, barrel chest, thoracic kyphoscoliosis, hypogonadism, and hypospadias. Phenotypic variation even within different sibships was considerable. The unique combination of the phenotypic characteristics prompted us to determine the shared homozygosity regions in patient genomes and the pathogenic variants by next generation technologies like single nucleotide polymorphism (SNP) genotyping and whole exome sequencing (WES). Through these analyses, we detected homozygous OBSL1 c.848delG (p.Gly283AlafsTer54) as the causal variant. Biallelic variants in OBSL1 are known to cause Three M Syndrome 2 (3M2), a rare disorder of growth retardation with characteristic facial dysmorphism and musculoskeletal abnormalities. Affected members of the family do not have the 3M2 hallmark features of dolichocephaly, hypoplastic midface, anteverted nares, low nasal bridge, pectus excavatum, sacral hyperlordosis, spina bifida occulta, anterior wedging of thoracic vertebrae, prominent heels, and prominent talus. Moreover, they have some variable features not typical for the syndrome such as round face, disproportionate short stature, barrel chest, thoracic kyphoscoliosis, hypogonadism, and hypospadias. Our study facilitated genetic diagnosis in the family, expanded the clinical phenotype for 3M2, and unraveled the considerable clinical variation within the same kinship. We conclude that unbiased molecular analyses such as WES should be more integrated into healthcare, particularly in populations with high parental consanguinity, given the potential of such analyses to facilitate diagnosis.
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spelling pubmed-105248102023-09-29 Expanding OBSL1 Mutation Phenotype: Disproportionate Short Stature, Barrel Chest, Thoracic Kyphoscoliosis, Hypogonadism, and Hypospadias Koprulu, Mine Shabbir, Rana Muhammad Kamran Mumtaz, Sara Tolun, Aslıhan Malik, Sajid Yale J Biol Med Case Report We present a Pakistani kinship afflicted with a syndrome with features including short stature, reduced sitting height, orofacial symptoms including prominent forehead and thick eyebrows, short and broad thorax, and variable features such as long philtrum, short broad neck, barrel chest, thoracic kyphoscoliosis, hypogonadism, and hypospadias. Phenotypic variation even within different sibships was considerable. The unique combination of the phenotypic characteristics prompted us to determine the shared homozygosity regions in patient genomes and the pathogenic variants by next generation technologies like single nucleotide polymorphism (SNP) genotyping and whole exome sequencing (WES). Through these analyses, we detected homozygous OBSL1 c.848delG (p.Gly283AlafsTer54) as the causal variant. Biallelic variants in OBSL1 are known to cause Three M Syndrome 2 (3M2), a rare disorder of growth retardation with characteristic facial dysmorphism and musculoskeletal abnormalities. Affected members of the family do not have the 3M2 hallmark features of dolichocephaly, hypoplastic midface, anteverted nares, low nasal bridge, pectus excavatum, sacral hyperlordosis, spina bifida occulta, anterior wedging of thoracic vertebrae, prominent heels, and prominent talus. Moreover, they have some variable features not typical for the syndrome such as round face, disproportionate short stature, barrel chest, thoracic kyphoscoliosis, hypogonadism, and hypospadias. Our study facilitated genetic diagnosis in the family, expanded the clinical phenotype for 3M2, and unraveled the considerable clinical variation within the same kinship. We conclude that unbiased molecular analyses such as WES should be more integrated into healthcare, particularly in populations with high parental consanguinity, given the potential of such analyses to facilitate diagnosis. YJBM 2023-09-29 /pmc/articles/PMC10524810/ /pubmed/37780995 http://dx.doi.org/10.59249/RLAU6003 Text en Copyright ©2023, Yale Journal of Biology and Medicine https://creativecommons.org/licenses/by-nc/4.0/This is an open access article distributed under the terms of the Creative Commons CC BY-NC license, which permits use, distribution, and reproduction in any medium, provided the original work is properly cited. You may not use the material for commercial purposes.
spellingShingle Case Report
Koprulu, Mine
Shabbir, Rana Muhammad Kamran
Mumtaz, Sara
Tolun, Aslıhan
Malik, Sajid
Expanding OBSL1 Mutation Phenotype: Disproportionate Short Stature, Barrel Chest, Thoracic Kyphoscoliosis, Hypogonadism, and Hypospadias
title Expanding OBSL1 Mutation Phenotype: Disproportionate Short Stature, Barrel Chest, Thoracic Kyphoscoliosis, Hypogonadism, and Hypospadias
title_full Expanding OBSL1 Mutation Phenotype: Disproportionate Short Stature, Barrel Chest, Thoracic Kyphoscoliosis, Hypogonadism, and Hypospadias
title_fullStr Expanding OBSL1 Mutation Phenotype: Disproportionate Short Stature, Barrel Chest, Thoracic Kyphoscoliosis, Hypogonadism, and Hypospadias
title_full_unstemmed Expanding OBSL1 Mutation Phenotype: Disproportionate Short Stature, Barrel Chest, Thoracic Kyphoscoliosis, Hypogonadism, and Hypospadias
title_short Expanding OBSL1 Mutation Phenotype: Disproportionate Short Stature, Barrel Chest, Thoracic Kyphoscoliosis, Hypogonadism, and Hypospadias
title_sort expanding obsl1 mutation phenotype: disproportionate short stature, barrel chest, thoracic kyphoscoliosis, hypogonadism, and hypospadias
topic Case Report
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10524810/
https://www.ncbi.nlm.nih.gov/pubmed/37780995
http://dx.doi.org/10.59249/RLAU6003
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