TY - JOUR
T1 - Prenatal diagnosis of lanosterol synthase deficiency
T2 - Fetal ultrasound findings as a window on family genetics
AU - Matza Porges, Sigal
AU - Mor-Shaked, Hagar
AU - Shaag, Avraham
AU - Porat, Shay
AU - Daum, Hagit
N1 - Publisher Copyright:
© 2023 Elsevier Masson SAS
PY - 2023/10
Y1 - 2023/10
N2 - Cholesterol is essential in the brain from the earliest stages of embryonic development. Disruption of cholesterol synthesis pathways that leads to cholesterol deficiency underlies a few syndromes, including desmosterolosis and Smith–Lemli–Opitz syndrome. In both syndromes, brain anomalies can occur. The LSS gene encodes lanosterol synthase (LSS), an important enzyme in the cholesterol biosynthesis pathway. Biallelic pathogenic variants in this gene cause alopecia–intellectual disability type 4 syndrome (APMR4, MIM 618840), a rare autosomal recessive disorder. Here, we describe two new LSS variants (c.1016C > T; p. Ser339Leu and c.1522G > C; p. Gly508Arg) found in a compound heterozygous fetus diagnosed prenatally with brain abnormalities by ultrasound scanning. Two of his siblings from the same parents also harbored these variants. Both siblings had alopecia, mild intellectual disability, autism spectrum disorder, and cataracts. To the best of our knowledge, this case represents the first prenatal diagnosis of APMR4 first suspected by ultrasound. In addition, the phenotypic features of the siblings are extensive compared with those described in previous reports and include abnormal corpus callosum, cataracts, alopecia, and developmental delay.
AB - Cholesterol is essential in the brain from the earliest stages of embryonic development. Disruption of cholesterol synthesis pathways that leads to cholesterol deficiency underlies a few syndromes, including desmosterolosis and Smith–Lemli–Opitz syndrome. In both syndromes, brain anomalies can occur. The LSS gene encodes lanosterol synthase (LSS), an important enzyme in the cholesterol biosynthesis pathway. Biallelic pathogenic variants in this gene cause alopecia–intellectual disability type 4 syndrome (APMR4, MIM 618840), a rare autosomal recessive disorder. Here, we describe two new LSS variants (c.1016C > T; p. Ser339Leu and c.1522G > C; p. Gly508Arg) found in a compound heterozygous fetus diagnosed prenatally with brain abnormalities by ultrasound scanning. Two of his siblings from the same parents also harbored these variants. Both siblings had alopecia, mild intellectual disability, autism spectrum disorder, and cataracts. To the best of our knowledge, this case represents the first prenatal diagnosis of APMR4 first suspected by ultrasound. In addition, the phenotypic features of the siblings are extensive compared with those described in previous reports and include abnormal corpus callosum, cataracts, alopecia, and developmental delay.
KW - Congenital alopecia
KW - Congenital cataracts
KW - Exome sequencing
KW - LSS pathogenic variant
KW - Prenatal diagnosis
KW - Ultrasound scanning
UR - http://www.scopus.com/inward/record.url?scp=85169840883&partnerID=8YFLogxK
U2 - 10.1016/j.ejmg.2023.104825
DO - 10.1016/j.ejmg.2023.104825
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C2 - 37659595
AN - SCOPUS:85169840883
SN - 1769-7212
VL - 66
JO - European Journal of Medical Genetics
JF - European Journal of Medical Genetics
IS - 10
M1 - 104825
ER -