Al‐Gazali Skeletal Dysplasia Constitutes the Lethal End of ADAMTSL2‐Related Disorders
ABSTRACT Lethal short‐limb skeletal dysplasia Al‐Gazali type (OMIM %601356), also called dysplastic cortical hyperostosis, Al‐Gazali type, is an ultra‐rare disorder previously reported in only three unrelated individuals. The genetic etiology for Al‐Gazali skeletal dysplasia has up until now been un...
Saved in:
Published in | Journal of bone and mineral research Vol. 38; no. 5; pp. 692 - 706 |
---|---|
Main Authors | , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , |
Format | Journal Article |
Language | English |
Published |
Hoboken, USA
John Wiley & Sons, Inc
01.05.2023
Wiley Subscription Services, Inc |
Subjects | |
Online Access | Get full text |
Cover
Loading…
Summary: | ABSTRACT
Lethal short‐limb skeletal dysplasia Al‐Gazali type (OMIM %601356), also called dysplastic cortical hyperostosis, Al‐Gazali type, is an ultra‐rare disorder previously reported in only three unrelated individuals. The genetic etiology for Al‐Gazali skeletal dysplasia has up until now been unknown. Through international collaborative efforts involving seven clinical centers worldwide, a cohort of nine patients with clinical and radiographic features consistent with short‐limb skeletal dysplasia Al‐Gazali type was collected. The affected individuals presented with moderate intrauterine growth restriction, relative macrocephaly, hypertrichosis, large anterior fontanelle, short neck, short and stiff limbs with small hands and feet, severe brachydactyly, and generalized bone sclerosis with mild platyspondyly. Biallelic disease‐causing variants in ADAMTSL2 were detected using massively parallel sequencing (MPS) and Sanger sequencing techniques. Six individuals were compound heterozygous and one individual was homozygous for pathogenic variants in ADAMTSL2. In one of the families, pathogenic variants were detected in parental samples only. Overall, this study sheds light on the genetic cause of Al‐Gazali skeletal dysplasia and identifies it as a semi‐lethal part of the spectrum of ADAMTSL2‐related disorders. Furthermore, we highlight the importance of meticulous analysis of the pseudogene region of ADAMTSL2 where disease‐causing variants might be located. © 2023 The Authors. Journal of Bone and Mineral Research published by Wiley Periodicals LLC on behalf of American Society for Bone and Mineral Research (ASBMR). |
---|---|
Bibliography: | ObjectType-Article-1 SourceType-Scholarly Journals-1 ObjectType-Feature-2 content type line 23 |
ISSN: | 0884-0431 1523-4681 1523-4681 |
DOI: | 10.1002/jbmr.4799 |