Preprint Review Version 1 Preserved in Portico This version is not peer-reviewed

Linear Skin Defects with Multiple Congenital Anomalies (LSDMCA): an unconventional mitochondrial disorder

Version 1 : Received: 18 December 2020 / Approved: 21 December 2020 / Online: 21 December 2020 (12:03:53 CET)

A peer-reviewed article of this Preprint also exists.

Indrieri, A.; Franco, B. Linear Skin Defects with Multiple Congenital Anomalies (LSDMCA): An Unconventional Mitochondrial Disorder. Genes 2021, 12, 263. Indrieri, A.; Franco, B. Linear Skin Defects with Multiple Congenital Anomalies (LSDMCA): An Unconventional Mitochondrial Disorder. Genes 2021, 12, 263.

Journal reference: Genes 2021, 12, 263
DOI: 10.3390/genes12020263

Abstract

Mitochondrial disorders, although heterogeneous, are traditionally described as conditions characterized by encephalomyopathy, hypotonia and progressive postnatal organ failure. Here we provide a systematic review of Linear Skin Defects with Multiple Congenital Anomalies (LSDMCA), a rare unconventional mitochondrial disorder which presents as a developmental disease; its main clinical features include microphthalmia with different degrees of severity, linear skin lesions, and central nervous system malformations. The molecular basis of this disorder has been elusive for several years. Mutations were eventually identified in three X-linked genes, i.e., HCCS, COX7B, and NDUFB11, which are all endowed with defined roles in the mitochondrial respiratory chain. A peculiar feature of this condition is its inheritance pattern: X-linked dominant male-lethal. Only female or XX male individuals can be observed, implying that nullisomy for these transcripts is incompatible with normal embryonic development in mammals. All three genes undergo X-inactivation that, according to our hypothesis, may contribute to the extreme variable expressivity observed in this condition. We propose that mitochondrial dysfunction should be considered as an underlying cause in developmental disorders. Moreover, LSDMCA should be taken into consideration by clinicians when dealing with patients with microphthalmia with or without associated skin phenotypes.

Subject Areas

MLS/MIDAS/LSDMCA, X-inactivation, HCCS/COX7B/NDUFB11, mitochondrial disorders, mitochondrial respiratory chain, microphthalmia, linear skin defects

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