Background: Leukodystrophies are a heterogeneous group of disorders affecting the white matter of the central nervous system, with or without affecting the peripheral nervous system. Biallelic variants in DEGS1 , coding for desaturase 1 (Des1) protein, were recently reported to be associated with hypomyelinating leukodystrophy (HLD), a subclass of leukodystrophies where the formation of the myelin sheath is affected. Methods Genomic sequencing was performed on our index patient with severe developmental delay, severe failure to thrive, dystonia, seizures, and hypomyelination on brain imaging. Sphingolipid analysis was performed and dihydroceramide/ceramide (dhCer/Cer) ratios were obtained by the measurement of ceramide and dihydroceramide species. Results A homozygous missense variant was identified in DEGS1 (c.565A &gt; G:p Asn189Asp). The identified DEGS1 variant has been annotated as “conflicting reports of pathogenicity” on ClinVar. Follow-up sphingolipid analysis on our patient showed significantly raised dhCer/Cer and this was consistent with dysfunction of the Des1 protein, providing additional evidence to support the pathogenicity of this variant. Conclusion While rare, pathogenic variants in DEGS1 should be considered in patients with HLD phenotype. To date, 25 patients have been reported across four studies on DEGS1 -related HLD, and, in this report, we summarize the literature. More such reports will enable deeper phenotypic characterization of this disorder.

Melissa Song Ting Wong

Terrence Thomas

Jiin Ying Lim

Sylvia Kam

Jing Xian Teo

Jianhong Ching

Chew Yin Jasmine Goh

Saumya Shekhar Jamuar

Weng Khong Lim

Ai Ling Koh

Clinical Dysmorphology

CLINICAL DYSMORPHOLOGY 发表关于出生缺陷的病因、临床描述、遗传图谱和分子胚胎学的简明病例报告。该杂志涵盖了多种先天性异常综合征等主题——特别强调了以前未描述的情况、罕见的发现、现有综合征的种族差异、胎儿异常和可能为发育基因定位提供线索的细胞遗传学异常。常规功能包括原创的、同行评审的文章、会议报告、书籍和软件评论、来自英国变形学俱乐部的摘要和摘要，以及文献摘要。提交的文章经过编辑的初步审查。有些文章可能会在没有进一步考虑的情况下退回给作者。那些被考虑出版的人将接受编辑的进一步评估和同行评审，以及那些被邀请从审稿人库中这样做的人。

Clinical Dysmorphology publishes concise case reports on the etiology, clinical descriptions, genetic mapping, and molecular embryology of birth defects. The journal covers a variety of congenital anomaly syndromes, with a particular emphasis on previously unreported conditions, rare findings, ethnic variations of existing syndromes, fetal abnormalities, and cytogenetic anomalies that may provide clues for developmental gene localization. Regular features include original, peer-reviewed articles, conference reports, book and software reviews, abstracts from the British Dysmorphology Club, and literature summaries. Submitted articles undergo preliminary editorial review, and some may be returned to authors without further consideration. Those considered for publication will undergo further editorial assessment and peer review, with reviewers invited from a pool of reviewers.

《Clinical Dysmorphology》发表关于出生缺陷的病因、临床特征、遗传图谱和分子胚胎学的简明病例报告。该杂志涵盖多种先天性异常综合征，特别强调以前未描述的情况、罕见发现、现有综合征的种族差异、胎儿异常以及可能为发育基因定位提供线索的细胞遗传学异常。常规功能包括原创的、经过同行评审的文章、会议报告、书籍和软件评论、来自英国变形学俱乐部的摘要，以及文献综述。提交的文章经过编辑的初步审查，有些文章可能会在没有进一步考虑的情况下退回给作者。那些被考虑出版的文章将接受编辑的进一步评估和同行评审，审稿人将从审稿人库中邀请。

Category	Quartile
医学	4
医学, 遗传学	4

DEGS1-related leukodystrophy: a clinical report and review of literature

ivySCI AI Smartly Parses PDF, Answers Researchers' Questions, and Helps You Understand Papers in Seconds

Journal Info

Category	Quartile
GENETICS & HEREDITY	4